The Matter of Kidney Biopsy in Monoclonal Gammopathy of Renal Significance: A Case Report of a New Pattern of Immunoglobulin-Storing Histiocytosis.

Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders, characterized by paraproteinemia which causes renal damage. These disorders never meet the diagnostic criteria for multiple myeloma (MM) or lymphoproliferative disease. Crystal-storing histiocytosis is one of the rarest patterns of MGRS, characterized by an accumulation of light chains of crystals within histiocyte's cytoplasm, located in bone marrow or other extramedullary sites such as the kidney, cornea, or thyme. A very few cases have been described as immunoglobulin-storing histiocytosis (IgSH) without evidence of crystals. In the recent literature, only 3 cases of IgSH have been described so far, none renal. In all cases, these very peculiar histopathological patterns are associated with lymphoproliferative or plasma cellular disorders. Here, we report a very unusual IgSH pattern in a kidney biopsy, which led to prompt detection and early therapeutic intervention, in a patient with otherwise misdiagnosed MGRS.

Clinical outcomes and temporal trends of immunological and non-immunological rare diseases in adult kidney transplant.

BACKGROUND: Rare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs. METHODS: Retrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT). RESULTS: Among 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8-11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups. CONCLUSIONS: Kidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients' and graft survival.

Detection of urinary podocytes by flow cytometry in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (iMN) is considered an immune-mediated disease where circulating autoantibodies against podocyte targets (mainly the PLA2R) cause the deposition of in-situ subepithelial immune-complexes. The consequent podocyte damage may cause cell detachment in urine (Podocyturia-PdoU). PdoU has been assessed in different kidney diseases, but limited data are available in iMN. In this study all patients with a diagnosis of iMN between 15/12/1999-16/07/2014 were tested for PLA2R antibodies (Ab anti-PLA2R, ELISA kit) and PdoU by flow cytometry with anti-podocalyxin antibody. A semi-quantitative PdoU score was defined according to the percentage of podocalyxin positive cells normalized to the total volume of sample and set relative to the urine creatinine measured in the supernatant. PdoU was positive in 17/27 patients (63%; 1+ score in 6/27-22.2%, 2+ in 4/27-14.8%, 3+ in 2/27-7.4%, 4+ in 5/27-18.5%). Only 2/7 patients with complete remission showed a positive PdoU (1+) while all six patients without remission have significant PdoU. PdoU+ was statistically correlated with the absence of remission and Ab anti-PLA2R + (p < 0.05) but PdoU, analysed as a continuous variable, showed a non-linear correlation with proteinuria or PLA2R antibody levels also in the cohort of patients with two available PdoU tests. In conclusion, PdoU could be detected in iMN and seems to be associated with commonly considered markers of disease activity (proteinuria and Ab anti-PLA2R) with a non-linear correlation. Despite data should be confirmed in large and prospective cohorts, according to the podocyte depletion hypothesis PdoU may represent an early marker of immunological activation with potential prognostic utility.

[Renal Infarction: multicentric cases in Piedmont].

We describe factors associated to renal infarction, clinical, instrumental and laboratoristic features, and therapeutic strategies too. This is an observational, review and polycentric study of cases in Nephrologic Units in Piedmont during 2013-2015, with diagnosis of renal infarction by Computed Tomography Angiography (CTA). We collected 48 cases (25 M, age 57±16i; 23 F age 70±18, p = 0.007), subdivided in 3 groups based on etiology: group 1: cardio-embolic (n=19) ; group 2: coagulation abnormalities (n= 9); group 3: other causes or idiopathic (n=20). Median time from symptoms to diagnosis, known only in 38 cases, was 2 days (range 2 hours- 8 days). Symptoms of clinical presentation were: fever (67%), arterial hypertension (58%), abdominal o lumbar pain (54%), nausea/vomiting (58%), neurological symptoms (12%), gross hematuria (10%). LDH were increased (>530 UI/ml) in 96% of cases (45 cases out of 47), PCR (>0.5 mg/dl) in 94% of cases (45 out of 48), and eGFR <60 ml/min in 56% of cases (27 out of 48). Comparison of the various characteristics of the three groups shows: significantly older age (p=0.0001) in group 1 (76±12 years) vs group 2 (54±17 years) and group 3 (56±17 years); significantly more frequent cigarette smoking (p = 0.01) in group 2 (67%; 5 cases out of 9) and group 3 (60%; 12 cases out of 20) than group 1 (17%). No case has been subjected to endovascular thrombolysis. In 40 out of 48 cases, anticoagulant therapy was performed after diagnosis: in 12 (32%) cases no treatment, in 12 cases (30%) heparin, in 8 cases (20%) low molecular weight heparin, in 4 cases (10%) oral anticoagulants, in 3 cases fondaparinux (7%), in 1 case (2%) dermatan sulfate. CONCLUSIONS: Although some characteristics may guide the diagnosis, latency between onset and diagnosis is still moderately high and is likely to affect timely therapy.

Mitochondrial neurogastrointestinal encephalomyopathy treated with peritoneal dialysis and bone marrow transplantation.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease caused by thymidine phosphorylase deficiency which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). It lacks an established treatment and the prognosis is traditionally poor. We report a case of a young female patient with normal renal function and MNGIE treated by peritoneal dialysis (PD) and allogeneic bone marrow transplantation (BMT). PD was effective in reducing dThd and dUrd plasma levels and in improving clinical symptoms. To our knowledge, this is the first report on the beneficial effects of PD regarding MNGIE neurological symptoms. PD, therefore, should be considered especially in medically compromised patients as a supportive treatment to improve clinical conditions before BMT.

Impact of contrast-induced acute kidney injury definition on clinical outcomes.

BACKGROUND: Contrast-induced acute kidney injury (CIAKI) is a frequent complication after infusion of contrast media in patients undergoing percutaneous coronary intervention. A wide range of CIAKI rates occurs after intervention between 3% and 30%, depending on the definition. The aim of this study was to identify which methodology was more effective at recognizing patients at high risk for in-hospital and out-of-hospital adverse events. METHODS AND RESULTS: Serum creatinine increases, after contrast agent infusion, were evaluated in 755 consecutive and unselected patients. Incidences of CIAKI diagnosed by 2 common definitions varied from 6.9% (creatinine increase of ≥0.5 mg/dL, CIAKI-0.5) to 15.9% (creatinine increase of ≥25%, CIAKI-25%). Significant differences appeared between the 2 definitions of sensitivity to predict renal failure according to receiver operating characteristic curve analysis (98% for CIAKI-0.5 and 62% for CIAKI-25%), using a cutoff value of postprocedural glomerular filtration rate of 60 mL/min. Both definitions of CIAKI were related to composite adverse events, but CIAKI-0.5 showed a stronger predicting value (odds ratio 2.875 vs 1.802, P = .036). In multivariate linear regression, only CIAKI-0.5 was a predictive variable of death (odds ratio 3.174, 95% CI 1.368-7.361). CONCLUSIONS: An increase in serum creatinine of ≥0.5 mg/dL is more sensitive because it recognizes more selectively those patients with a higher risk of mortality and morbidity. Serum creatinine increases of ≥25% overestimate CIAKI by including many patients without postprocedural relevant deterioration of renal function and affected by a lower risk of adverse events at follow-up.

[Application of guidelines in clinical practice: a multicenter analysis of the treatment of membranous glomerulonephritis in Piedmont, Italy]. / Applicazione delle linee-guida nella realta' clinica: indagine multicentrica sul trattamento della glomerulonefrite membranosa in Piemonte.

The treatment of membranous glomerulonephritis (MGN) is controversial, especially in cases of no response to first-line treatment or multiple relapses. The Clinical Nephrology Group of Piedmont carried out a multicenter analysis of the treatment of patients affected by MGN in 15 nephrology units in Piedmont. The first treatment is usually started after a waiting period of 3-6 months in case of proteinuria in the nephrotic range but normal or slightly impaired renal function. A history of cancer, the presence of infectious disease, and secondary forms of MGN are criteria for exclusion from treatment. As first-line treatment, Piedmont nephrologists prescribe corticosteroids alternated with immunosuppressive drugs, generally preferring cyclophosphamide to chlorambucil. Only one nephrology unit uses cyclosporin A (CyA) as the first choice. In case of no response to treatment, a second therapeutic approach is undertaken after 2-12 months. Second-line treatment consists of CyA if immunosuppressive drugs were given before, and corticosteroids/ immunosuppressive drugs if CyA was the first treatment. A further choice may be ACTH or rituximab. In case of multiple relapses the treatment options are the same but previous immunosuppressive treatment, patient age, and the duration of kidney disease with a greater probability of renal failure and progression towards sclerosis require careful attention. Concern has been expressed regarding the potentially severe side effects of ACTH including myopathy, cataract and diabetes. In conclusion, the applied therapeutic approaches in Piedmont reflect the difficulty reported in the literature in identifying simple recommendations. ACTH and rituximab are increasingly preferred for the treatment of MGN and there is a need for prospective studies to determine the best protocol for rituximab and the safety profile of ACTH.

[Lymphomatous renal involvement]. / Il coinvolgimento renale nei linfomi.

The incidence of lymphomas, especially non-Hodgkin's lymphoma (NHL), has shown a steady increase over the last decades. At the same time, the prognosis has improved. Given the longer survival of lymphoma patients, pathological manifestations related to malignancy might become more frequent. In this setting, the kidney is one of the most important solid organs affected by direct or indirect lymphomatous involvement. Kidney involvement can be related to obstruction or treatment-induced toxicity, but more intriguing are 1) direct infiltration (NHL); 2) renal malignancies in patients affected by Hodgkin's disease or NHL; 3) associated glomerular diseases. Primary infiltration is rarely seen, while secondary infiltration is described most frequently in autopsy series, even in the absence of renal failure. These alterations may mimic glomerular and/or interstitial disease. The association with kidney malignancies, mostly renal cell carcinoma but also urothelial tumors in Hodgkin''s disease, is higher in lymphoma patients than in the general population: the relative risk at 10 years is about 1.5. Glomerulonephritis is described in patients with Hodgkin's disease or NHL; in the former minimal change disease is most frequent, in the latter the glomerular pattern varies widely. Glomerulonephritis can precede, be concurrent with, or follow lymphoma manifestations. Renal biopsy is often needed in this setting.

Cholesterol crystal embolism syndrome in dialysis patients: an emerging clinical diagnosis?

BACKGROUND: Cholesterol crystal embolism syndrome (CCE) is an increasing end-stage renal disease cause. Few cases have been described on dialysis, despite the high prevalence of the predisposing factors. METHODS: The diagnostic criteria of the present study were: skin lesions, myalgia, fatigue, fever and acute inflammatory serologic signs, in the presence of severe vasculopathy. The precipitating factors were: anticoagulation, endovascular intervention and ulcerated atherosclerotic plaque. RESULTS: Between October 2003 and September 2005, CCE was diagnosed in 6 dialysis patients (of 200-210 on chronic treatment): 5 males, 1 female, median age 59.5 years (47-70) and end-stage renal disease follow-up 11.5 years (3-25). All had severe vasculopathy, 5 cardiopathy, and 4 were failed graft recipients. The treatment included: peritoneal dialysis, daily dialysis, 'conventional' hemodialysis (2 cases) and hemodiafiltration. The diagnosis was based on the clinical-laboratory picture in 1 patient. In the 5 others clues were present (dicumarol therapy, angioplasty, femoral artery thrombosis, CCE predialysis and ulcerated aortic plaque). The therapeutic approach consisted of corticosteroids (5 cases), statins (4 cases) and prostaglandin analogues (4 cases). CONCLUSION: The differential diagnosis of CCE should also be considered in dialysis patients (necrotic lesions, limb pain and vasculitis-like signs).

Efficacy of an educational programme for secondary school students on opinions on renal transplantation and organ donation: a randomized controlled trial.

CONTEXT: Organ shortage for transplantation is a crucial problem; educational interventions may increase donations and decrease opposition. OBJECTIVE: To test the efficacy of an educational programme on opinions on organ transplantation and kidney donation. DESIGN AND PARTICIPANTS: Cluster Randomized Controlled Trial: eight intervention and eight control schools were randomly selected from the 33 public schools that agreed to participate. Targets: students in the last 2 years of secondary school (17-18 years); seven schools per group completed the study. EDUCATIONAL PROGRAMME: INTERVENTION: first questionnaire (anonymous); 2 h lesson in each class; 2 h general session with patients and experts; second questionnaire. CONTROL: questionnaires. MAIN OUTCOME MEASURES: Differences between questionnaires (comparative analysis); interest; satisfaction with the programme; (cross-sectional analysis). RESULTS: 1776 first, 1467 second questionnaires were retrieved. Living kidney donation: at baseline 78.8% of students would donate a kidney to a relative/friend in need. The answers were unaffected by type of school but depended on sex (females more prone to donate, P<0.001); the answers did not change after the lessons. Cadaveric kidney donation: baseline opinions were mixed (intervention schools: 31.5% yes, 33.7% no, 34.8% uncertain), depending on type of school (classical-scientific high schools more positive than technical institutes, P<0.001), sex (males more prone to donate, P<0.001). Answers on living and cadaveric donation were correlated (P<0.001). The educational intervention increased favourable (31.5 to 42.9%) and uncertain (34.8 to 41.1%) opinions and decreased negative ones (33.7 to 16%) (P<0.001). CONCLUSIONS: Educational interventions are effective in increasing interest and improving opinions about cadaveric organ donation.

Dialysis choice in the context of an early referral policy: there is room for self care.

BACKGROUND: Predialysis care is vital for the patient and is crucial for dialysis choice: empowered, early referred patients tend to prefer out-of-hospital and self-care treatment; despite these claims, early referral remains too often a program more than a reality. Aim of the study was to evaluate the pattern and reasons for RRT choice in patients treated in a long-standing outpatient network, presently following 850 chronic patients (about 80% diabetics), working with an early referral policy and offering a wide set of dialysis options (home hemo and PD; self care and limited care hemodialysis; hospital hemodialysis). METHODS: Prospective historical study. All patients who started RRT in January 2001-December 2003 were considered. Correlations between demographical (sex, age, educational level) or clinical variables (pre-RRT follow-up, comorbidity, SGA and Karnofsky) and treatment choice have been tested by univariate (chi-square, Kruskal-Wallis) and multivariate models (logistic regression), both considering all choices and dichotomising choice into "hospital" versus "out of hospital dialysis". RESULTS: Hospital dialysis was chosen by 32.6% of patients; out of hospital in 67.4% (PD 26.5%, limited-care 18.4%, home hemodialysis 4.1%, self-care 18.4%). Hospital dialysis and PD were chosen by elderly patients (median age: 67.5 and 70 years respectively) with multiple comorbidities (75% and 92.3%); no difference for age, comorbidity, Karnofsky, SGA and educational level. 6/13 PD patients needed the help of a partner. Self-care/home hemodialysis patients were younger (median age 52), had higher educational level (p = 0.014) and lower prevalence of comorbidity (63.6% vs 94.7% in the other dialysis patients, p = 0.006). In the context of a long follow-up period (3.9 years) a statistically significant difference was found comparing hospital dialysis (3.3 years) vs out of hospital dialysis (4.9 years) (p = 0.035). In a logistic regression model, only pre-RRT follow-up was correlated with dialysis "hospital vs "out of hospital" choice (p = 0.014). CONCLUSION: Early nephrological follow-up may enhance self and home-based dialysis care.