Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by a genetic dysregulation of the alternative complement pathway, characterized by thrombocytopenia, hemolytic anemia, and acute kidney injury, and included in the group of thrombotic microangiopathies. With the introduction of humanized monoclonal antibodies that inhibit C5 activation, the natural history of aHUS completely changed, with a better prognosis, a quick recovery of renal function, and a significant reduction of end-stage renal disease incidence. Nowadays, there is an increasing interest in the molecular and genetic bases of this severe disease. The aim of this narrative review is to provide readers with a practical guide about different possible involved genes, elucidating the specific role of each transcribed protein in the pathogenesis of aHUS. Moreover, we analyzed the main current evidence about the relationship among genetic mutations, outcomes, and the risk of recurrence of this manifold disease.

Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. We investigated sex-specific disparities in CKD-related complications and mortality according to estimated glomerular filtration rate (eGFR) levels. We analyzed National Health and Nutrition Examination Survey (NHANES) data spanning from 1999 to 2018, including adult participants with an eGFR of 15–150 mL/min/1.73 m². The outcomes were CKD-related complications [hypertension, anaemia, cardiovascular (CV) diseases, acidosis, hyperphosphatemia, hyperparathyroidism] and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios and hazard ratios for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. The study included 49 558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR–hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women). Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier; women show a steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

Background: Kidney stone disease (KSD) is characterized by an increasing prevalence worldwide, representing an important clinical issue and a financial burden for healthcare systems. A KSD-causing monogenic variant is traditionally expected in up to 30% of children and 1–5% of adults forming stones, confirmed by a strong connection between a positive family history and KSD. The insufficient use of genetic testing in these patients is associated with a lack of perceived benefit and a scarce awareness of inherited kidney diseases. Genetic testing has important practical implications, such as the possibility of earlier diagnoses, familial counseling, and tailored therapy, based on the evaluation of fine-mapped pathogenic variants. Our aim is to analyze the current evidence on genetic testing in KSD patients to whom genetic tests were applied without strict a priori selection criteria, to provide an overview of its diagnostic yield and factors potentially affecting it (such as the age of KSD onset, a familial history of KSD, consanguinity, and extrarenal features). Methods: A literature review was performed, selecting original articles published in the last 10 years concerning genetic investigations in patients affected by nephrolithiasis or nephrocalcinosis. Available data were subsequently extracted and analyzed. Results: In total, 13 studies on 1675 patients (77% pediatric populations) were included; 333 patients were determined to be affected by a monogenic disorder, with an overall yield of about 20%. The likelihood of a positive genetic finding was much higher in pediatric (26%) than adult populations (8%). Cystinuria was the most common diagnosis in both populations. After the removal of conditions that could be identified with a stone composition analysis or urinary chemistry investigation, the diagnostic yield dropped to 19% among pediatric patients and below 5% for adults. Conclusions: Genetic testing should be considered in KSD pediatric patients and in selected subgroups of adults with suggestive features when a diagnosis is not established after stone examination and blood as well as urine metabolic profiling.

Summary In a peritoneal dialysis longitudinal cohort, REMS and DXA showed similar bone density, but only DXA detected significant cortical bone loss. REMS tended to give lower bone mineral density values and did not correlate with DXA changes. REMS may complement DXA when DXA findings are difficult to interpret or when closer longitudinal monitoring is needed, but larger studies are needed to define its role. Background Dual X-ray absorptiometry (DXA) is the gold standard for bone mineral density (BMD) assessment in chronic kidney disease patients, but it can have limited accuracy and radiofrequency echographic multi-spectrometry (REMS) may overcome some of its limitations. We aimed to evaluate and compare longitudinal BMD changes assessed by DXA and REMS in peritoneal dialysis (PD) patients. Methods Prospective cohort study including 20 PD patients that underwent two separate DXA and REMS evaluations. Clinical, biochemical, and imaging data, including abdominal aorta calcification (AAC) scores and fracture history, were collected. Longitudinal BMD changes were analyzed using linear mixed-effects models. Results Over a median follow-up period of 19.8 months, DXA revealed significant BMD declines at the femoral neck (FN) (−3.2%, p = 0.039) while REMS showed non-significant numerical declines. REMS consistently yielded lower BMD values than DXA at both lumbar spine (LS) and FN. The trajectories of BMD over time were similar between DXA and REMS for LS (p = 0.806) and FN (p = 0.229), regardless of whether patients were receiving anti-osteoporosis treatment and of the presence of fractures. However, there was no correlation of the annualized changes in BMD at the FN and LS between the two methods (r² = 0.001, p = 0.905, and r² = 0.001, p = 0.928, respectively). Conclusion DXA detected a significant decline in BMD at cortical sites, whereas REMS did not, and the correlation of the annualized changes between the two methods in assessing changes over time was poor. Given the small sample size, larger studies are needed to clarify the comparative and possible complementary roles of REMS and DXA in monitoring bone health in end-stage kidney disease.

Background: The prevalence of kidney stones tends to increase worldwide due to dietary and climate changes. Disease management involves a high consumption of healthcare system resources which can be reduced with primary prevention measures and prophylaxis of recurrences. In this field, collaboration between general practitioners (GPs) and hospitals is crucial. Methods: a panel composed of general practitioners and academic and hospital clinicians expert in the treatment of urinary stones met with the aim of identifying the activities that require the participation of the GP in the management process of the kidney stone patient. Results: Collaboration between GP and hospital was found crucial in the treatment of renal colic and its infectious complications, expulsive treatment of ureteral stones, chemolysis of uric acid stones, long-term follow-up after active treatment of urinary stones, prevention of recurrence and primary prevention in the general population. Conclusions: The role of the GP is crucial in the management and prevention of urinary stones. Community hospitals which are normally led by GPs in liaison with consultants and other health professional can have a role in assisting multidisciplinary working as extended primary care.

Background: Kidney stone formation is driven by an imbalance between lithogenic substances and crystallization inhibitors. Current guidelines recommend a 24-h urine collection in patients with kidney stone disease to assess the risk of stone formation and monitor therapy compliance. However, real-world data on adherence to these guidelines remain limited and outdated. Methods: We used the Health Search Database to examine laboratory test data of patients with kidney stone disease between 2013 and 2022 in Italy. Adults with at least one episode of kidney or ureteral stones during this period were included. We used the prescription of urinary calcium, oxalate, and citrate levels as a proxy for full metabolic testing. Results: A total of 21,907 adult patients were identified (44.6% women). Only 4.8% ( n = 1059) underwent 24-h urine testing, and just 0.6% had all three target measurements. Testing rates were slightly higher in recurrent stone formers (6.1%). The likelihood of receiving a test increased nearly sixfold after a nephrology visit (OR 6.09, 95% CI 5.27–7.05, p < 0.001), compared to a lower increase after urology visits (OR 1.95, 95% CI 1.71–2.23, p < 0.001). Nonetheless, fewer than 10% of kidney stone disease patients consulted a nephrologist, and only half of those with coexisting chronic kidney disease (CKD) had such a referral. Conclusion: Awareness of 24-h urine testing and nephrology referral in stone formers remains low, despite their role in guiding personalized treatment. Promoting their use could enhance patient care by identifying urinary abnormalities and reducing the risk of recurrence and complications. Graphical