Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update.

BACKGROUND: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. METHODS: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)]. RESULTS: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). CONCLUSION: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Preventing Continuous Renal Replacement Therapy-Induced Hypophosphatemia: An Extended Clinical Experience with a Phosphate-Containing Solution in the Setting of Regional Citrate Anticoagulation.

AIMS: To evaluate the efficacy and safety of a commercially available phosphate-containing solution for continuous renal replacement therapy (CRRT) in preventing CRRT-related hypophosphatemia. METHODS: In heart surgery patients undergoing continuous veno-venous haemodiafiltration (CVVHDF) with regional citrate anticoagulation (RCA), we combined an 18 mmol/l citrate solution with a phosphate-containing (1.2 mmol/l) dialysate/replacement fluid evaluating the incidence of hypophosphatemia and the need for parenteral phosphorus supplementation. RESULTS: In 75 patients on RCA-CVVHDF, the mean filter life was 53.9 ± 33.6 h. Regardless of baseline levels, phosphoremia was progressively corrected and maintained in a narrow normality range throughout RCA-CRRT days (after 72 h: 1.14 ± 0.25 mmol/l). Considering the whole CRRT period, 45 out of 975 (4.6%) serum phosphorus determinations met the criteria for mild (<0.81 mmol/l) or moderate (<0.61 mmol/l) hypophosphatemia; severe hypophosphatemia (<0.32 mmol/l) never occurred. After 72 h 88% of the patients were normophosphatemic, 9% hyperphosphatemic and 3% hypophosphatemic. CONCLUSIONS: RCA-CVVHDF with a phosphate-containing solution enabled the maintenance of phosphorus levels within normophosphatemic range in most of the patients, minimizing the occurrence of CRRT-related hypophosphatemia.

Severe acute kidney injury following cardiac surgery: short-term outcomes in patients undergoing continuous renal replacement therapy (CRRT).

BACKGROUND: Acute kidney injury (AKI) represents a major complication of cardiac surgery. Our aim was to evaluate, in patients undergoing continuous renal replacement therapy (CRRT) for cardiac surgery-associated AKI (CS-AKI), prognostic factors related to in-hospital survival and renal function recovery to independence from RRT. METHODS: We conducted a retrospective analysis in patients with severe CS-AKI who underwent CRRT for at least 48 h. The sequential organ failure assessment (SOFA) score was calculated on a daily basis to evaluate illness severity throughout the intensive care unit (ICU) stay. RESULTS: In 264 patients (age 66.4 ± 11.7 years, 192 males), 30-day survival was 57.6 % while survival to discharge from the hospital was 40.5 %. Renal function recovery occurred in 96.3 % of survivors and in 13.4 % of non-survivors (p < 0.001). Multivariate analysis selected advancing age, oliguria, sepsis and the highest level of SOFA score within the first week of CRRT (SOFA-max) as independent prognostic factors for failure to recover renal function. Female gender was associated with a higher probability of survival, while higher serum creatinine at the start of CRRT, oliguria, sepsis and SOFA-max were independently associated with mortality. The subgroup of patients with a day-1 SOFA score above the median (≥10) showed a lower probability of survival and a lower cumulative incidence of renal function recovery. CONCLUSIONS: In a selected population of patients with severe CS-AKI requiring RRT, short-term outcomes appear strongly associated with the worst grade of illness severity during the first week of CRRT, thus reflecting the sequential occurrence of additional major complications during ICU stay. Renal function recovery and in-hospital survival appear mutually linked, sharing oliguria, sepsis and SOFA score as the main determinants of both outcomes.

Continuous veno-venous hemofiltration using a phosphate-containing replacement fluid in the setting of regional citrate anticoagulation.

PURPOSE: The need for prolonged anticoagulation and the occurrence of hypophosphatemia are well known drawbacks of continuous renal replacement therapies (CRRT). The aim was to evaluate the effects on acid-base status and serum phosphate of a regional citrate anticoagulation (RCA) protocol for continuous veno-venous hemofiltration (CVVH) combining the use of citrate with a phosphate-containing replacement fluid. METHODS: In a small cohort of heart surgery patients undergoing CRRT for acute kidney injury, we adopted an RCA-CVVH protocol based on a commercially available citrate solution (18 mmol/l) combined with a recently introduced phosphate-containing replacement fluid (HCO3 -30 mmol/l, phosphate 1.2), aimed at preventing phosphate depletion. RESULTS: In 10 high bleeding-risk patients, the RCA-CVVH protocol provided an adequate circuit lifetime (46.8 ± 30.3 h) despite the adoption of a low citrate dose and a higher than usual target circuit Ca2+ (≤0.5 mmol/l). Acid-base status was adequately maintained without the need for additional interventions on RCA-CVVH parameters and without indirect sign of citrate accumulation [(pH 7.43 (7.41-7.47), bicarbonate 24.4 mmol/l (23.2-25.6), BE 0 (-1.5 to 1.1), calcium ratio 1.97 (1.82-2.01); median (IQR)]. Serum phosphate was steadily maintained in a narrow range throughout RCA-CVVH days [1.1 mmol/l (0.9-1.4)]. A low amount of phosphorus supplementation (0.9 ± 2 g/day) was required in only 30% of patients. CONCLUSIONS: Although needing further evaluation, the proposed RCA-CVVH protocol ensured a safe and effective RCA without electrolyte and/or acid-base derangements. CRRT-induced hypophosphatemia was prevented in most of the patients by the adoption of a phosphate-containing replacement solution, minimizing phosphate supplementation needs.

Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid-base status and phosphate supplementation needs.

BACKGROUND: Recent guidelines suggest the adoption of regional citrate anticoagulation (RCA) as first choice CRRT anticoagulation modality in patients without contraindications for citrate. Regardless of the anticoagulation protocol, hypophosphatemia represents a potential drawback of CRRT which could be prevented by the adoption of phosphate-containing CRRT solutions. The aim was to evaluate the effects on acid-base status and phosphate supplementation needs of a new RCA protocol for Continuous Venovenous Hemodiafiltration (CVVHDF) combining the use of citrate with a phosphate-containing CRRT solution. METHODS: To refine our routine RCA-CVVH protocol (12 mmol/l citrate, HCO3- 32 mmol/l replacement fluid) (protocol A) and to prevent CRRT-related hypophosphatemia, we introduced a new RCA-CVVHDF protocol (protocol B) combining an 18 mmol/l citrate solution with a phosphate-containing dialysate/replacement fluid (HCO3- 30 mmol/l, Phosphate 1.2). A low citrate dose (2.5-3 mmol/l) and a higher than usual target circuit-Ca(2+) (≤ 0.5 mmol/l) have been adopted. RESULTS: Two historical groups of heart surgery patients (n = 40) underwent RCA-CRRT with protocol A (n = 20, 102 circuits, total running time 5283 hours) or protocol B (n = 20, 138 circuits, total running time 7308 hours). Despite higher circuit-Ca(2+) in protocol B (0.37 vs 0.42 mmol/l, p < 0.001), circuit life was comparable (51.8 ± 36.5 vs 53 ± 32.6 hours). Protocol A required additional bicarbonate supplementation (6 ± 6.4 mmol/h) in 90% of patients while protocol B ensured appropriate acid-base balance without additional interventions: pH 7.43 (7.40-7.46), Bicarbonate 25.3 (23.8-26.6) mmol/l, BE 0.9 (-0.8 to +2.4); median (IQR). No episodes of clinically relevant metabolic alkalosis, requiring modifications of RCA-CRRT settings, were observed. Phosphate supplementation was needed in all group A patients (3.4 ± 2.4 g/day) and in only 30% of group B patients (0.5 ± 1.5 g/day). Hypophosphatemia developed in 75% and 30% of group A and group B patients, respectively. Serum phosphate was significantly higher in protocol B patients (P < 0.001) and, differently to protocol A, appeared to be steadily maintained in near normal range (0.97-1.45 mmol/l, IQR). CONCLUSIONS: The proposed RCA-CVVHDF protocol ensured appropriate acid-base balance without additional interventions, providing prolonged filter life despite adoption of a higher target circuit-Ca(2+). The introduction of a phosphate-containing solution, in the setting of RCA, significantly reduced CRRT-related phosphate depletion.

Regional citrate anticoagulation in CVVH: a new protocol combining citrate solution with a phosphate-containing replacement fluid.

Regional citrate anticoagulation (RCA) is a valid anticoagulation method in continuous renal replacement therapies (CRRT) and different combination of citrate and CRRT solutions can affect acid-base balance. Regardless of the anticoagulation protocol, hypophosphatemia occurs frequently in CRRT. In this case report, we evaluated safety and effects on acid-base balance of a new RCA- continuous veno-venous hemofiltration (CVVH) protocol using an 18 mmol/L citrate solution combined with a phosphate-containing replacement fluid. In our center, RCA-CVVH is routinely performed with a 12 mmol/L citrate solution and a postdilution replacement fluid with bicarbonate (protocol A). In case of persistent acidosis, not related to citrate accumulation, bicarbonate infusion is scheduled. In order to optimize buffers balance, a new protocol has been designed using recently introduced solutions: 18 mmol/L citrate solution, phosphate-containing postdilution replacement fluid with bicarbonate (protocol B). In a cardiac surgery patient with acute kidney injury, acid-base status and electrolytes have been evaluated comparing protocol A (five circuits, 301 hours) vs. protocol B (two circuits, 97 hours): pH 7.39 ± 0.03 vs. 7.44 ± 0.03 (P < 0.0001), bicarbonate 22.3 ± 1.8 vs. 22.6 ± 1.4 mmol/L (NS), Base excess -2.8 ± 2.1 vs. -1.6 ± 1.2 (P = 0.007), phosphate 0.85 ± 0.2 vs. 1.3 ± 0.5 mmol/L (P = 0.027). Protocol A required bicarbonate and sodium phosphate infusion (8.9 ± 2.8 mmol/h and 5 g/day, respectively) while protocol B allowed to stop both supplementations. In comparison to protocol A, protocol B allowed to adequately control acid-base status without additional bicarbonate infusion and in absence of alkalosis, despite the use of a standard bicarbonate concentration replacement solution. Furthermore, the combination of a phosphate-containing replacement fluid appeared effective to prevent hypophosphatemia.

[Pharmacokinetics of antibiotics in continuous renal replacement therapies (CRRT)]. / Farmacocinetica degli antibiotici nelle terapie sostitutive renali continue (CRRT).

In the critically ill patient, acute kidney injury (AKI) is frequently associated with infective complications requiring appropriate antimicrobial treatment. AKI and multiple organ dysfunction syndrome can affect the pharmacokinetic parameters of many drugs. Furthermore, the start of renal replacement therapy (RRT) is an additional variable to be taken into consideration to avoid inappropriate antimicrobial therapy. Continuous renal replacement therapies (CRRT) are widely adopted in the intensive care unit (ICU) and antibiotics that are significantly eliminated by the kidney are likely to be removed during RRT. Generally, drug-dosing adjustments are required if the extracorporeal clearance accounts for more than 25-30% of the total body clearance. The molecular weight cutoffs of the more widely used membranes are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the antibiotics most commonly used in ICU patients. However, CRRTs are still not standardized and the impact of RRT on plasma drug concentrations can be substantially different depending on the CRRT modality (diffusive, convective or both), membrane characteristics and delivered dialysis dose. In any case, drug-dosing adjustments should be based on the knowledge of the pharmacokinetic and pharmacodynamic properties of the different classes of antimicrobials, taking into account that high extracorporeal clearances could lead to drug underexposure in clinical conditions where appropriate antibiotic treatment is essential.

Regional citrate anticoagulation in cardiac surgery patients at high risk of bleeding: a continuous veno-venous hemofiltration protocol with a low concentration citrate solution.

INTRODUCTION: Regional citrate anticoagulation (RCA) is a valid option in patients at high risk of bleeding who are undergoing continuous renal replacement therapy (CRRT). The aim of this study was to evaluate, in critically ill patients with severe acute kidney injury following cardiac surgery, the efficacy and safety of RCA-continuous veno-venous hemofiltration (CVVH) using a low concentration citrate solution. METHODS: In high bleeding-risk cardiac surgery patients, we adopted, as an alternative to heparin or no anticoagulation, RCA-CVVH using a 12 mmol/l citrate solution. For RCA-CVVH settings, we developed a mathematical model to roughly estimate citrate load and calcium loss. In order to minimize calcium chloride supplementation, a calcium-containing solution was used as post-dilution replacement fluid. RESULTS: Thirty-three patients (age 70.8 ± 9.5, Sequential Organ Failure Assessment (SOFA) score 13.9 ± 2.5) were switched to RCA-CVVH from no anticoagulation CRRT. Among them, 16 patients had been previously switched from heparin to no anticoagulation because of bleeding or heparin-related complications. RCA-CVVH filter life (49.8 ± 35.4 hours, median 41, 152 circuits) was significantly longer (P < 0.0001) when compared with heparin (30.6 ± 24.3 hours, median 22, 73 circuits) or no anticoagulation (25.7 ± 21.2 hours, median 20, 77 circuits). Target circuit and systemic Ca(++) were easily maintained (0.37 ± 0.09 and 1.18 ± 0.13 mmol/l), while the persistence of a mild metabolic acidosis required bicarbonate supplementation (5.8 ± 5.9 mmol/hours) in 27 patients. The probability of circuit running at 24, 48, 72 hours was higher during RCA-CVVH (P < 0.0001), with a lower discrepancy between delivered and prescribed CRRT dose (P < 0.0001). RCA was associated with a lower transfusion rate (P < 0.02). Platelet count (P = 0.012) and antithrombin III activity (P = 0.004) increased throughout RCA-CVVH, reducing the need for supplementation. CONCLUSIONS: RCA safely prolonged filter life while decreasing CRRT downtime, transfusion rates and supplementation needs for antithrombin III and platelets. In cardiac surgery patients with severe multiple organ dysfunction syndrome, the adoption of a 12 mmol/l citrate solution may provide a suboptimal buffers supply, easily overwhelmed by bicarbonate supplementation.

Incidence of contrast-induced acute kidney injury associated with diagnostic or interventional coronary angiography.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) represents an important cause of hospital-acquired AKI. The aim of this study was to evaluate the incidence of CI-AKI after coronary angiography (CA) or percutaneous coronary intervention (PCI) and the role of patient-/procedure-related risk factors. METHODS: For 11 months, patients undergoing CA or PCI were prospectively evaluated for CI-AKI, and factors possibly affecting CI-AKI were analyzed. Statistical analysis was completed using Student's t-test, chi-square or Fisher exact test, and multivariate logistic regression. RESULTS: Among 585 consecutive patients, incidence of CI-AKI was 5.1% (n=30) and renal replacement therapy was required in 10% of those (n=3). Incidence of CI-AKI was higher in patients with anemia or chronic kidney disease (CKD) associated with diabetes. Basal hemoglobin was significantly lower in CI-AKI patients while Mehran score, contrast medium (CM) volume, contrast ratio (CM volume / maximum contrast dose) and ratio glomerular filtration rate (CM volume / GFR) were significantly higher. Multivariate analysis selected a higher contrast ratio as a factor independently associated with a higher risk of CI-AKI which otherwise appeared to be lower with increasing basal hemoglobin. CONCLUSIONS: The incidence of CI-AKI after CA or PCI was higher in patients with CKD associated with diabetes. Lower levels of basal hemoglobin appeared to be related to a higher risk of CI-AKI, and contrast media volume, especially if exceeding the dose adjusted for renal function, was a strong modifiable risk factor for CI-AKI.

[Regional citrate anticoagulation: towards a first-choice treatment]. / Anticoagulazione regionale con citrato: verso un trattamento di prima scelta.

Continuous renal replacement therapy (CRRT) is the most widely used technique for the treatment of severe acute kidney injury in the critically ill. The need for prolonged anticoagulation is the most important drawback of CRRT and clinically important bleeding significantly increases the risk of death. Therefore, alternative anticoagulation methods should be more widely adopted. Among the potential alternatives to systemic heparin anticoagulation, regional citrate anticoagulation (RCA) is the most promising. By reducing ionized calcium inside the extracorporeal circuit, citrate is able to block the coagulation cascade at different levels. Compared with unfractionated heparin, several studies reported better filter survival times and a marked reduction of transfusion rates with RCA. Despite the positive reports about the efficacy and safety of RCA, the use of this alternative method of anticoagulation appears to be relatively limited. Desirable future improvements in RCA should be focused on simplifying protocols, minimizing the need for calcium and magnesium supplementation, increasing the flexibility of buffer balance, and introducing customized dialysis systems able to deliver automated RCA. In particular, safe protocols with automated delivery of citrate and calcium can allow easy parameter settings that can be adapted to a wide range of clinical situations, facilitating the wider use of RCA in the coming years.

Choroidopathy in patients with systemic lupus erythematosus with or without nephropathy.

BACKGROUND: The aim of this study was to evaluate indocyanine green angiographic findings in patients with systemic lupus erythematosus (SLE) with or without lupus nephritis. In particular, the presence of choroidal abnormalities at indocyanine green angiography (ICG-A) that could not be detected by fluorescein angiography (FAG) was investigated. METHODS: Sixteen patients with SLE underwent simultaneous ICG-A and FAG. Patients were divided into 2 groups based on whether renal disease was present (group A, n=9) or not (group B, n=7). RESULTS: Drusen-like deposits were ophthalmoscopically evident in only 1 out of 9 group A patients (11.1%). While FAG disclosed the deposits in 4 out of 9 group A patients (44.4%), drusen-like deposits were otherwise found in all group A patients (100%) by ICG-A. FAG and ICG-A did not show choroidal alterations in group B patients. CONCLUSIONS: ICG-A can provide information that is not detectable by clinical or FAG examination in patients with lupus nephritis (group A). The findings of choroidopathy by ICG-A represent an indicator of ocular involvement and could be an indirect sign of renal involvement. Given that histological lesions may be present where there are no anomalies in urinary sediment and/or proteinuria, the positivity of ICG-A could help in deciding whether or not to carry out a renal biopsy. Therefore, ICG-A could be useful in the screening of patients with SLE, especially where there are no evident signs of renal involvement.

Failure of mycophenolate mofetil therapy in primary refractory nephrotic syndrome.

Mycophenolate mofetil (MMF) has been suggested as a promising therapeutic agent in the treatment of idiopathic nephrotic syndrome. Two patients with persistent nephrotic syndrome, secondary to minimal change disease and idiopathic membranous nephropathy, respectively, who were steroid-, cyclophosphamide- and cyclosporine-resistant, were treated with MMF during a 6-12-month period. In these cases there was no beneficial effect from treatment with MMF. Therapy was stopped after 6 months in case 1 and after 12 months in case 2 due to the persistence of proteinuria.

Is Cronkhite-Canada Syndrome necessarily a late-onset disease?

Cronkhite-Canada Syndrome is a non-inherited, non-congenital disease characterized by juvenile hamartomatous gastrointestinal polyps with a typically late onset. In the case described herein the disease was diagnosed in a 17-year-old male with type I diabetes and thalassaemia minor, in coincidence with severe symptomatic intestinal candidiasis. Following the disappearance of the mycosis and correction of the protein and electrolyte imbalance, the ectodermal abnormalities returned to normal and the patient remained asymptomatic during a 7-year follow-up period, despite proteinuria resulting from membranous glomerulopathy. The concept that Cronkhite-Canada Syndrome is a late-onset disease should probably be reconsidered as it may remain asymptomatic, and thus not diagnosed, for a long a time.

Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding.

BACKGROUND: The ongoing necessity for systemic heparinization is a well-known disadvantage of continuous renal replacement therapies (CRRT), and alternative methods of anticoagulation may be required. Our aim was to evaluate, in patients with a high risk of bleeding, the possibility of an acceptable filter life with non-anticoagulation CRRT and, in case of early filter failure, the efficacy and safety of bedside monitored regional anticoagulation with heparin and protamine. METHODS: Fifty-nine patients underwent CRRT for acute renal failure (ARF) following cardiac surgery. Patients who fulfilled one of the following criteria were selected for non-anticoagulation CRRT: spontaneous bleeding, aPTT > 45 sec, thrombocytopenia and recent surgery (< 48 hr). Filter life < 24 hr without anticoagulation was the cut-off point for starting the regional anticoagulation CRRT. Heparin was infused pre-filter and protamine post-filter at an initial ratio of 1 mg protamine:100 IU heparin. The ratio was adjusted to achieve a patient aPTT < 45 sec and a circuit > 55 sec. RESULTS: Twenty-two (37.3%) patients had been selected for non-anticoagulation. Of them, 12 patients continued to receive non-anticoagulation (filter life: 38.3 +/- 30.5 hr) while 10 switched to regional anticoagulation (filter life: 38.6 +/- 25 hr). During regional anticoagulation no statistical difference was found between baseline aPTT (36.7 +/- 6.4 sec) and patient aPTT (41.5 +/- 12.6 sec) while circuit aPTT (77.7 +/- 43.3 sec) was significantly higher than patient aPTT (p < 0.0001). The probabilities of the circuits remaining free from clotting after 24, 48 and 72 hr were: a) non-anticoagulation: 55.5%, 30.1% and 16.6%, b) regional anticoagulation: 76.2%, 39.6% and 19.8%. There was no rebound anticoagulation observed after regional anticoagulation CRRT ended. CONCLUSIONS: Non-anticoagulation CRRT allowed an adequate filter life in most patients with a high risk of bleeding for prolonged aPTT and/or thrombocytopenia. Despite concerns regarding the need for careful monitoring, regional anticoagulation with heparin and protamine can be considered as a safe and valid alternative when non-anticoagulation is unsuitable because of early filter failure.

Antiendomysial antibodies in Berger's disease.

The finding of increased levels of immunoglobulin A (IgA) against food antigens in patients with IgA nephropathy prompted the hypothesis of an association between IgA nephropathy and celiac disease (CD). Attention was initially directed to antigliadin antibodies, then to IgA antiendomysial antibodies (IgA-EMA). IgG1-EMA have been found in patients with CD with IgA-EMA-negative results. The presence of IgA- and IgG1-EMA was investigated in 36 patients with IgA nephropathy, 15 patients with other primary glomerulonephritis, and 15 patients with lupus nephritis. IgA-EMA and IgG1-EMA were detected by indirect immunofluorescence analysis. At the time of renal biopsy, the following factors were evaluated: history of macroscopic hematuria, serum creatinine level, urinalysis, 24-hour proteinuria, blood pressure, and histological classification of IgA nephropathy. Sixteen of 36 patients with IgA nephropathy (44.4%) showed EMA positivity. Among patients with positive EMA, 12 patients (75%) were IgG1-EMA positive, 2 patients (12.5%) were IgA-EMA positive, and 2 patients (12.5%) were positive for both isotypes. No significant differences were observed between the two groups (EMA positive versus EMA negative) concerning age, serum creatinine level, macroscopic hematuria, blood pressure, 24-hour proteinuria, or degree of renal histological involvement. IgA- and IgG1-EMA were not detected in patients with other primary nephropathies or lupus nephritis. These results, based on the finding of IgG1-EMA, suggest a common pathogenetic pathway for CD and IgA nephropathy. On this basis, the presence of IgG1-EMA and/or IgA-EMA should be investigated in patients with IgA nephropathy. Furthermore, the role of a gluten-free diet in the natural history of IgA nephropathy, at least in EMA-positive patients, needs to be ascertained.