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Background and objectives: End stage renal disease (ESRD) patients are exposed to the risk of ionizing radiation during repeated imaging studies. The variability in diagnostic imaging policies and the accompanying radiation doses across various renal units is still unknown. We studied this variability at the centre level and quantified the associated radiation doses at the patient level. Methods: Fourteen Italian nephrology departments enrolled 739 patients on haemodialysis and 486 kidney transplant patients. The details of the radiological procedures performed over one year were recorded. The effective doses and organ doses of radiation were estimated for each patient using standardized methods to convert exposure parameters into effective and organ doses Results: Computed tomography (CT) was the major contributor (> 77%) to ionizing radiation exposure. Among the haemodialysis and kidney transplant patients, 15% and 6% were in the high (≥ 20mSv per year) radiation dose groups, respectively. In haemodialysis patients, the most exposed organs were the liver (16mSv), the kidney (15mSv) and the stomach (14mSv), while the uterus (6.2mSv), the lung (5.7mSv) and the liver (5.5mSv) were the most exposed in kidney transplant patients. The average cumulative effective dose (CED) of ionizing radiation among centres in this study was highly variable both in haemodialysis (from 6.4 to 18.8mSv per patient-year; p = 0.018) and even more so in kidney transplant (from 0.6 to 13.7mSv per patient-year; p = 0.002) patients. Conclusions: Radiation exposure attributable to medical imaging is high in distinct subgroups of haemodialysis and transplant patients. Furthermore, there is high inter-centre variability in radiation exposure, suggesting that nephrology units have substantially different clinical policies for the application of diagnostic imaging studies.

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 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.

Contains fulltext : 232930.pdf (Publisher’s version ) (Closed access) BACKGROUND: On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS: In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p < 0.001 ) and gender ( χ 2 17.3; p < 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality OR = 3.40 (2.40-4.82), while the OR for a RDW > 13.7 % was 4.09 (2.87-5.83); a platelet count > 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Background The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.

ImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. ObjectiveTo derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and ParticipantsWe derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and MeasuresCox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R-D(2) measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. ResultsThe study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R-D(2) (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and RelevanceIn this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

BACKGROUND Kidney transplantation is the treatment of choice to restore fertility to women on renal replacement therapy. Over time, immunosuppressive, support therapies and approaches towards high-risk pregnancies have changed. The aim of this study was to analyse maternal-foetal outcomes in two cohorts of transplanted women who delivered a live-born baby in Italy in 1978-2013, dichotomized into delivery before and after January 2000. METHODS A survey involving all the Italian transplant centres was carried out, gathering data on all pregnancies recorded since the start of activity at each centre; the estimated nationwide coverage was 75%. Data on cause of ESRD, dialysis, living/cadaveric transplantation, drug therapy, comorbidity, and the main maternal-foetal outcomes were recorded and reviewed. Data were compared with a low-risk cohort of pregnancies from two large Italian centres (2000-14; Torino and Cagliari Observational Study cohort). RESULTS The database consists of 222 pregnancies with live-born babies after transplantation (83 before 2000 and 139 in 2000-13; 68 and 121 with baseline and birth data, respectively), and 1418 low-risk controls. The age of the patients significantly increased over time (1978-99: age 30.7 ± 3.7 versus 34.1 ± 3.7 in 2000-13; P < 0.001). Azathioprine, steroids and cyclosporine A were the main drugs employed in the first time period, while tacrolimus emerged in the second. The prevalence of early preterm babies increased from 13.4% in the first to 27.1% in the second period (P = 0.049), while late-preterm babies non-significantly decreased (38.8 versus 33.1%), thus leaving the prevalence of all preterm babies almost unchanged (52.2 and 60.2%; P = 0.372). Babies below the 5th percentile decreased over time (22.2 versus 9.6%; P = 0.036). In spite of high prematurity rates, no neonatal deaths occurred after 2000. The results in kidney transplant patients are significantly different from controls both considering all cases [preterm delivery: 57.3 versus 6.3%; early preterm: 22.2 versus 0.9%; small for gestational age (SGA): 14 versus 4.5%; P < 0.001] and considering only transplant patients with normal kidney function [preterm delivery: 35 versus 6.3%; early preterm: 10 versus 0.9%; SGA: 23.7 versus 4.5% (P < 0.001); risks increase across CKD stages]. Kidney function remained stable in most of the patients up to 6 months after delivery. Multiple regression analysis performed on the transplant cohort highlights a higher risk of preterm delivery in later CKD stages, an increase in preterm delivery and a decrease in SGA across periods. CONCLUSIONS Pregnancy after transplantation has a higher risk of adverse outcomes compared with the general population. Over time, the incidence of SGA babies decreased while the incidence of 'early preterm' babies increased. Although acknowledging the differences in therapy (cyclosporine versus tacrolimus) and in maternal age (significantly increased), the decrease in SGA and the increase in prematurity may be explained by an obstetric policy favouring earlier delivery against the risk of foetal growth restriction.

We report the case of a 48-year-old male, whose musculoskeletal manifestations, previously related to long-term renal replacement therapy (RRT), were diagnosed as ankylosing spondylitis when symptoms changed their pattern on daily hemodialysis (DHD). The patient started RRT in 1981; in 1985 he received a cadaver graft, which failed in 1987. Secondary hyperparathyroidism, amyloid geoids, bilateral carpal tunnel syndrome and high aluminium levels were present. Musculoskeletal pain, reported since 1986, involved feet, heels, hips, shoulders, hands, spine. Symptoms impairing daily life did not improve after parathyroidectomy. He developed chronic hypotension and recurrent atrial fibrillation. In 1994 and 1998, because of thoracic pain, coronarography was performed (normal on both occasions). In June 2000, DHD was started. Equivalent renal clearance increased from 9-12 to 15-17 mL/min. Well-being remarkably improved. In September 2000, musculoskeletal pain worsened and bilateral Achilles tendinitis occurred. The worsening of musculoskeletal symptoms despite the improvements in well-being and other dialysis related symptoms prompted a re-evaluation of the case. The diagnosis of ankylosing spondylitis was based on: history of plantar fasciitis, bilateral Achilles tendinitis, inflammatory spinal pain with limitation of lumbar spine mobility (positive Schober test), radiological evidence of grade 2 bilateral sacroiliitis, presence of HLA-B27. This diagnosis cast light on the episodes of chest pain, explained by enthesopathy at the costosternal and manubriosternal joints and atrial fibrillation, due to HLA-B27 associated impairment in heart conduction. This case exemplifies the difficulty of differential diagnosis of multisystem illness in patients with long RRT follow-up.

rac-2-Cyclopentylthio-6-[1-(2,6-difluorophenyl)ethyl]-3,4-dihydro-5-methylpyrimidin-4(3H)-one (MC-1047) is a potent inhibitor of HIV-1 multiplication in acutely infected cells. MC-1047 racemate has been resolved by chiral HPLC using, as chiral stationary phase (CSP), a commercially available (R,R)-Whelk-01 column. The optical purity and the circular dichroism (CD) of the two resolved enantiomers were determined and their biological activities tested in in vitro assays. Molecular modeling inspection of the binding of (R) and (S) enantiomers to the non-nucleoside binding site (NNBS) of reverse transcriptase (RT) using the defined model of F(2)-S-DABO/RT complex indicates the (R) enantiomer as the more active isomer.

Vascular complications are frequent in long-term dialysis patients. The differential diagnosis is complex and includes immunological derangement (underlying disease, uremia), vasculopathic-atheroembolic diseases, calciphylaxis, infections, neoplasm, coagulation disorders, and adverse drug effects.We report on a 50-year-old male patient with a long follow-up on renal replacement therapy (20 years), currently on daily hemodialysis. The patient's history of kidney transplantation was complicated by seven acute rejection episodes and by Kaposi sarcoma; comorbidity included HLA-B27 positive ankylosing spondylitis, diffuse vascular disease, recurrent atrial fibrillation, chronic hypotension, HCV positivity. Ten days after the start of warfarin for an atrial fibrillation episode, the patient developed digital necrotising ulcerations, rapidly evolving into partial symmetric digital gangrene at distal phalanxes. The timing and evolution of the lesions and the finding of protein S deficiency were the clues for diagnosing warfarin-induced skin necrosis (WISN); the drug was discontinued and therapy with low-molecular weight heparin, plasma and prostacyclin achieved slow resolution of lesions.According to a combined MEDLINE and EMBASE search, this is the first report of WISN in a hemodialysis patient: underlining the clinical relevance of this uncommon problem, this case exemplifies the difficult differential diagnosis of acute vascular skin lesions in dialysis

Urinalysis is a fundamental test in internal medicine and nephrology. Figures for costs are available in the general laboratory, where biochemical and microscopic urinalysis are commonly performed as semiautomated screening tests. Information on costs is lacking in the nephrology laboratory, where a time-consuming morphological analysis is usually preferred. This study analyses the costs of urinalysis in a nephrology laboratory.In the nephrology laboratory at the University of Turin - Italy, biochemical urinalysis consists of multi-property strip and proteinuria/creatininuria, done by laboratory technicians. Phase-contrast microscopy is done by a nephrologist or biologist. Time dedicated to the tests was recorded by the same operator over 20 working days, during which 350 urine samples were processed (median 19/day, range 842). The production costs were calculated with the logic bottom-up technique.Overall time needed was 11.9 minutes/sample. Biochemical urinalysis required 6.6 minutes/sample; time required and samples processed were inversely related (or =19 samples: 7.95 minutes/sample;19 samples: 5.6 minutes/sample, p=0.01). Microscopic urinalysis took 5.3 minutes/slide; the best time-to-samples ratio was at 18-22 samples per day (with peak efficiency at 21 samples: 4.6 minutes). Cost of reagents and disposables was Euro1.06/sample. Time accounted for euro 5.32/sample (technicians, nephrologist-biologist), with total direct cost of euro 6.38/sample.In a nephrology laboratory, microscopic urinalysis is a time-consuming, expensive test. Analysis of cost and modalities may be useful, in a time of budget constrains, to maintain a role for this precious semeiotic art.

A clinical audit is used to verify the application of evidence-based clinical guidelines. Our regional section of the Italian Society of Nephrology was the first to establish a region-based program of clinical audits of compliance with guidelines for treating osteodystrophy and anemia of patients on chronic dialysis. This study summarizes the main results of the 2 audits of the Piemonte region.Structured questionnaires were sent twice to all of the 22 dialysis centers of Piemonte and to the Center of Valle D'Aosta for an Audit on Osteodystrophy (in 2000 and 2004) and for the Audit on Anemia (2003). The questionnaires were meant to evaluate the clinical schedule of treatment relative to calcium-phosphate balance and anemia in dialysis patients.All centers responded, showing low levels of agreement with the targets of Italian guidelines. In sum, in 2000 only 27% of centers had more than 70% of patients with serum phosphate5.5 mg/dL, but that rate had increased to 33% in 2004. Only 35% (in 2000) and 40% (in 2004) of the centers had more than 90% of patients with Kt/V1.2. The Audit on Anemia showed a median of 42% of patients with hemoglobin between 11 and 12 g/dL, and only 2 centers had more than 70% of patients above this target.The first result of our pioneering experience was that we found that compliance with minimal levels of care was still inadequate, with regard to hyperphosphatemia, dialysis adequacy and anemia. Nevertheless, the 2nd Audit on Osteodystrophy showed a relative improvement in the results. But, most importantly, this open regional report has encouraged comparisons, and motivated centers to adopt a strategy of understanding, addressing and correcting inadequate levels of care, and furthermore increased satisfaction with the care being offered.

Kidney international 102(1), 160-172 (2022). doi:10.1016/j.kint.2022.02.042, Published by Elsevier, New York, NY

Objective Growth arrest-specific 6 (Gas6) and its receptors have been shown to play a crucial role in the homeostasis of the innate immune system by regulating apoptosis and inflammation. We aimed to verify whether an impairment of this system is associated with systemic lupus erythematosus (SLE) disease activity and with lupus nephritis (LN). Methods Plasma Gas6 and the soluble cleaved form of the receptors MerTK (sMer) and Axl (sAxl) concentrations were measured in n=59 SLE patients (n=44 with nephritis, 75%) and analysed in relationship to clinical and laboratory data. Results Patients with LN were characterised by higher Gas6 (19.0 ng/mL [16.8–24.5] vs. 16.5 ng/mL [13.89–18.91]; p=0.03) and sAxl plasma levels than those without LN (31.36 ng/mL [25.1–41.4] vs. 20.2 ng/mL [15.6–30.7]; p=0.03); conversely sMer plasma concentrations were similar between groups. All the three biomarkers studied were directly correlated to creatinine and daily proteinuria, being inversely related to creatinine clearance. 39 patients had a proteinuria level of