The risks associated with percutaneous native kidney biopsies: a prospective study.

BACKGROUND: The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. METHODS: The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. RESULTS: Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08-1.17], liver disease (OR 2.27, 95% CI 1.21-4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07-1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92-0.99) were protective. CONCLUSIONS: This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

The Role of Rituximab in Primary Focal Segmental Glomerular Sclerosis of the Adult.

Introduction: Primary focal segmental glomerular sclerosis (FSGS) is a rare, likely immune-mediated disease. Rituximab (RTX) may play a role in management, although data in adults are scanty. Methods: We collected cases of RTX-treated primary FSGS within the Italian Society of Nephrology Immunopathology Working Group and explored response rate (24-hour proteinuria <3.5 g and <50% compared with baseline, stable estimated glomerular filtration rate). Results: A total of 31 patients were followed for at least 12 months; further follow-up (median 17 months, interquartile range [IQR] 15-33.5) was available for 11. At first RTX administration, median creatinine and 24-hour proteinuria were 1.17 mg/dl (IQR 0.83-1.62) and 5.2 g (IQR 3.3-8.81), respectively. Response rate at 3, 6, and 12 months was 39%, 52%, and 42%, respectively. In the first 12 months, creatinine level remained stable whereas proteinuria and serum albumin level improved, with an increase in the proportion of patients tapering other immunosuppressants. There were 6 patients who were retreated with RTX within 12 months, either for proteinuria increase or refractory disease; only the 2 responders to the first RTX course experienced a further response. At univariate analysis, 6-month response was more frequent in steroid-dependent patients (odds ratio [OR] 7.7 [95% CI 1.16-52.17]) and those with proteinuria <5 g/24 h (OR 8.25 [1.45-46.86]). During long-term follow-up, 4 of 5 responders at 12 months maintained a sustained response, either without further immunosuppression (2 of 4) or with pre-emptive RTX (2 of 4); 1 relapsed and responded to RTX retreatment. Conclusion: RTX may be an option in primary FSGS, especially in steroid-dependent patients, with 24-hour proteinuria <5 g and previously responders to RTX. Optimal long-term management for responders is unclear, with some patients experiencing sustained remission and others requiring RTX retreatment, either preemptive or after rising proteinuria.

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial.

BACKGROUND: A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking. METHODS: We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events. RESULTS: At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen. CONCLUSIONS: This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535.

[Survey on the Prevalence of Rare Kidney Diseases in Sicily].

Renal Diseases represent almost 6% of all Rare Diseases but are often misdiagnosed. In a survey made in Sicily in 2016, based on cases reported from all public hospitals according to a list of rare kidney diseases, we were able to collect 337 cases (199 males and 138 females). The highest prevalence was detected in children: 13.9 cases in 100.000 children; the mean age was 10, and the median 5 years, at the time of the diagnosis. Comparing our data with those available in the Sicilian Register of Rare Diseases we found that only 141 cases (54%) were present in the register. Promoting regional registries of rare kidney diseases in Italy may be useful for epidemiologic studies.

Acute kidney injury in a patient with metabolic syndrome.

INTRODUCTION: The metabolic syndrome (MS) encompasses many metabolic abnormalities and the insulin resistance is considered as one of the most significant denominators. The chronic kidney disease (CKD) is an emerging health problem but only few patients would reach the end stage renal disease. There exists an increasing strong association between MS and CKD, but up until now the link between MS and CKD is unclear and there are few studies regarding the renal histology in MS. METHODS: We describe an acute tubulointerstitial nephritis case, due to both infective and pharmacological aetiology, overlapping relevant histological changes (focal segmental glomerulosclerosis [FSG], hyaline arteriosclerosis) in a patient with MS and previously normal renal function. Despite the severe vascular finding (elevated renal arterial resistive index), the patient recovered a normal renal function. RESULTS: We reviewed the kidney pathological studies in MS and analyzed the principal renal histological images of glomerulomegaly, segmental glomerulosclerosis, and obesity-related glomerulopathy. CONCLUSION: Despite the strong association, the renal involvement in MS has not been proven. A greater knowledge of the combination of histological renal changes in MS can help to understand the pathophysiological mechanism(s) of MS.

[Membranous glomerulonephritis with crescent overlapping]. / La Glomerulonefrite membranosa con sovrapposizione crescentica.

Acute crescentic transformation is a rare but well described event in patients with membranous glomerulonephritis. We report our experience with a 66-year-old Caucasian man presented for rapid decline in renal function. For nearly 10 years, he was suffering from hypertension and mixed sensori-motor polyneuropathy. He performed therapy with prednisone and azathioprine, suspended 1 year before presentation. Moreover, six months before presentation, laboratory tests showed a serum creatinine concentration 220 mol/L and a 24-h protein excretion 0,75 g/d. The physical examination showed oedema and severe hypertension; the 24-h protein excretion was 1,1 gr/d and creatinine concentration was 550.8 mol/L; ANCA and other immunological tests were negative. There was no evidence of SLE, infection or malignancy. The kidney biopsy highlighted a membranous GN with crescentic overlap. The patient was treated with steroid and cyclophosphamide. Because there was no sign of improvement after 2 months, we stopped the cyclophosphamide therapy and the patient started chronic haemodialysis treatment. Unlike membranous nephropathy, patients with superimposed crescentic glomerulonephritis appear to have a more aggressive clinical course. The importance of recognizing this group of patients with membranous nephropathy and crescentic glomerulonephritis is that immunosuppressive therapy may ameliorate the progression of renal damage and in some cases early treatment was associated with useful recovery of renal function.

Rapid response to high cut-off haemodialysis and bortezomib therapy in a patient with acute renal failure and plasma cells dyscrasia

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