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Background and Aims DRESS syndrome is a rare, idiosyncratic, potentially life-threatening adverse drug reaction, characterized by latent period after intake of the inciting drug (2-6 weeks), fever higher than 38.5°C, skin eruptions (usually pruritic maculopapular rash or diffuse erythematous eruption), eosinophilia (in 66-95% of patients), mononucleosis-like atypical lymphocytes (27-67% of pts), thrombocytopenia, lymphadenopathy (in 54% of pts) and multiple organ involvement. In 50-60% of patients, two or more organs are involved, most frequently liver (hepatomegaly, hepatitis with ALT> 2 times and ALP> 1,5 times the upper limit), kidney (acute interstitial nephritis, most often induced by allopurinol) and lung (interstitial pneumonia). Cardiovascular involvement occurs lately (up to four months after recovery) with myocarditis, decreased LV function and elevated troponin. Different mechanisms have been involved in the pathogenesis of DRESS syndrome, including detoxification defects leading to reactive metabolite formation and subsequent immunological reactions, slow acetylation and reactivation of human herpes, including Epstein-Barr virus and HHV-6. Cacoub et al reported 172 cases of DRESS: the most frequently reported “trigger-drugs” were carbamazepine, allopurinol, sulfasalazine, phenobarbital, nevirapine and HHV-6 infections were positive in 80% of cases. Interestingly, the culprit drug could be able to trigger viral reactivation, inducing a pathogenic anti-viral CD8+ response. According to available literature, the drug should be withdrawn and, in cases of visceral involvement, systemic steroids are indicated (1 mg/kg orally with slow taper over 3-6 months). In severe cases, other therapies include IVIG, plasmapheresis and immunosuppressant drugs. CASE REPORT A 72-year-old male, affected by ESKD in peritoneal dialysis and hypokinetic heart disease, started lenalidomide for multiple myeloma with bone involvement. After 18 days he presented a violet maculopapular rash involving >50% of his body, fever (38,5 °C), leukopenia with CRP <0,8 mg/dl. Lenalidomide was withdrawn and started oral steroid, anti-histamine and levofloxacin. One week later he was admitted for a syncopal episode. Laboratory tests revealed leukocytosis (12.250/mm), eosinophilia (until 56%, 4.550/mm) and cholestatic-cellular liver damage (ALT 1448 U/l, ALP 308 U/l) requiring albumin infusion. Extensive infectious and autoimmune workup was negative, including ANA test, immunological liver diseases tests, blood cultures, viral/bacterial tests, except for HHV6 reactivation (420 copies/ml). US abdominal study was negative, while DLCO test showed an important diffusive deficit. ECHO showed a reduced LV ejection. Skin biopsy demonstrated sparse vacuolization of epidermis and dermal-epidermal inflammation with some eosinophils and CD8+ T cells, suggesting a drug reaction. For clinic and laboratory features RegiSCAR score system and Japanese consensus group categorized this case as “definite DRESS” respectively with score 6 and 7. So we started IVIG (1 gr/Kg for 2 days) and prednisone with reduced dose for comorbidities (0,8 mg/Kg daily, tapered to 0,6 mg/Kg after 1 week); the patient gradually improved but after 1 week, DRESS syndrome relapsed with rash, elevated GOT and GPT and troponin until 330 ng/l with normal ECG; he has just started steroid bolus and IVIG. Conclusion The variety of drugs, the clinical course with slow resolution and relapse and HHV-6 reactivation suggest that drugs cannot be the sole etiology of DRESS. Precise mechanism of lenalidomide in DRESS syndrome is not clear and its immunomodulatory activity could contribute in the hypersensivity reaction. Only few cases are reported in literature, but with the increasing use of lenalidomide a broad workup and a careful approach are important for a fast diagnosis

Monoclonal gammopathies are associated with acute and chronic kidney injury. Nephrotoxicity of the secreted monoclonal (M)-protein is related to its biological properties and blood concentration. Little is known about epidemiology, clinical manifestations, and outcome of monoclonal gammopathies in patients with kidney disease. We retrospectively collected data about demographics, clinical manifestations, and renal histological lesions of all patients (n = 1334) who underwent kidney biopsy between January 2000 and March 2017. Monoclonal gammopathy was detected in 174 (13%) patients with a mean age of 66.4 ± 13.1 years. The spectrum of monoclonal gammopathies comprised monoclonal gammopathy of undetermined significate (MGUS) (52.8%), multiple myeloma (MM) (25.2%), primary amyloidosis (AL) (9.1%), smoldering MM (SMM) (4%), non-Hodgkin lymphoma (NHL) (6.8%), and Hodgkin lymphoma (HL) (1.7%). Monoclonal gammopathy of renal significance (MGRS) accounted for 6.5% in patients with MGUS and 14.2% in patients with SMM. Evaluation of kidney biopsy revealed that M-protein was directly involved in causing kidney injury in MM (93.1%). MM was the only gammopathy significantly associated with an increased risk of kidney injury (odds ratio [OR] = 47.5, CI 95%, 13.7–164.9; P ≤ 0.001 ). While there were no significant differences in the progression toward end-stage renal disease or dialysis P = 0.776 , monoclonal gammopathies were associated with a different risk of death P = 0.047 at the end of the follow-up. In conclusion, monoclonal gammopathy was a frequent finding (13%) in patients who underwent kidney biopsy. M-protein was secreted by both premalignant (56.8%) and malignant (43.2%) lymphoproliferative clones. Kidney biopsy had a key role in identifying MGRS in patients with MGUS (6.5%) and SMM (14.2%). Among monoclonal gammopathies, only MM was significantly associated with biopsy-proven kidney injury. The rate of end-stage renal disease or dialysis was similar among monoclonal gammopathies, whereas NHL, MM, and SMM showed a higher rate of deaths.

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BACKGROUND AND AIMS Although discontinuation of antiplatelet agents at least 5 days before kidney biopsy is recommended by most guidelines and commonly advised by nephrologists, the evidence behind this practice is very low. Indeed, few non-randomized studies previously showed a similar rate of bleeding after kidney biopsy in patients who received aspirin and those who did not. Withdrawal of antiplatelet agents has been associated with an immediate and substantial increase in cardiovascular events, especially in patients at risk for coronary heart disease. METHOD We conducted a single centre retrospective cross-sectional study comparing the risk of complications after percutaneous ultrasound-assisted native kidney biopsy in patients who received antiplatelet agents within 5 days from biopsy and those who did not; the study was approved by local Ethical Committee (protocol 1321/2020/OSS*/AOUMO). The main outcome was the difference in the proportion of major complications (any of the following: red blood cells transfusion, need for selective arterial embolization, surgical revision, nephrectomy). Secondary outcomes were: difference in the proportion of minor complications (drop in haemoglobin >2 g/dL, bladder tamponade, macrohematuria, need for angio-CT scan, hematoma >3 cm),  difference in the proportion of complications between patients who received antiplatelet agents within 48 h and those who received them within 3–5 days from biopsy, identification of independent factors predictive of major complication. RESULTS We analszed 769 percutaneous native kidney biopsies performed by nephrologists from 1 January 2010 to 31 December 2020 in 741 patients; 113 procedures (14.69%) were conducted under antiplatelet therapy (within 5 days from biopsy). Demographical, clinical and laboratory characteristics of the whole cohort and dividing patients according to antiplatelet therapy status (absent or within 5 days from biopsy) are reported in Table 1; most patients (83.17%) on antiplatelet were receiving low-dose aspirin. A single (or a combination of more) major complication occurred in 17/656 (2.59%) of patients without and in 4/113 (3.54%) patients with antiplatelet therapy, with non-significant difference between groups (percentage point difference 1%, 95% CI –2% to 4%, P = .57); no deaths were attributable to the biopsy procedure. There were 103/656 (15.7%) minor complications in patients without and 14/113 (12.39%) in patients with antiplatelet therapy, with non-significant difference between groups (percentage point difference 3%, 95% CI –10% to 4%, P = .37). In patients treated with antiplatelet within 5 days from biopsy, we encountered no significant difference in the proportion of major or minor complications in those who received therapy in the last 48 h or 3–5 days before the procedure. The final multivariate stepwise logistic regression model for the prediction of major complication included two variables (platelets <120*10^3, eGFR); the model was logit(p) = –2668 + 2383*(platelets < 120*10^3)-0036*eGFR,  where P is the probability of having a major complication after kidney biopsy (see Table 2 for univariate and multivariate analysis). This model produced an AUC of 0808 (95% CI 0.724–0.89). CONCLUSION Receiving anti-platelet therapy (in particular, low-dose aspirin) within 5 days from percutaneous native kidney biopsy did not increase the risk of major or minor complications in our cohort. Platelet count < 120*10^3/µL and lower eGFR were significantly associated with an increased risk for major complication.