Bone mineral density assessment in patients with cystinuria.

BACKGROUND: Cystinuria is a rare genetic disease characterized by impaired tubular transport of cystine. Clinical features of cystinuria mainly include nephrolithiasis and its complications, although cystinuric patients may present with other comorbidities. There are currently no data on bone features of patients with cystinuria. Our aim is to characterize bone mineral density (BMD) in cystinuria. METHODS: Our study included adult cystinuric patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 followed at 3 specialized outpatient clinics in Italy (Rome, Naples and Verona). Markers of bone turnover were analyzed in a centralized laboratory. Clinical, biochemical and dual-energy X-ray absorptiometry (DEXA) data were collected from September 2021 to December 2022. Linear regression models were used to evaluate statistically significant deviations from zero of Z-scores. RESULTS: Twenty-seven patients were included in the study. Mean (SD) age was 37 (15) years, 41% were women. Mean estimated glomerular filtration rate was 99 mL/min/1.73 m2. Serum parameters associated with bone turnover (parathyroid hormone, FGF23, calcium and phosphate) were all in the normal range, with only 4 patients showing mild hypophosphatemia. Prevalence of low bone mineral density, defined as Z-score ≤ - 2 at any site, was 15%. Average Z-scores were negative across most sites. CONCLUSIONS: Our study suggests that cystinuric patients have lower bone mineral density compared with individuals of the same sex and age, even when their kidney function is normal.

Renal Cystinuria and Immune Cells (T Lymphocytes) Dysfunction: What We Know about?

INTRODUCTION: Cystinuria (CYS) is the most common monogenic kidney stone disease. METHODS: Starting from an unusual case of CYS associated to primary sclerosing cholangitis, inflammatory bowel disease (IBD), and autoimmune hepatitis in a young male, we carefully review the literature and propose here a working hypothesis regarding the potential risk of cystinuric patients to develop conditions due to immune system dysregulation. To corroborate this hypothesis, we retrospectively evaluate the frequency of dysimmunity in a monocentric cohort including 36 cystinuric patients compared to healthy and disease controls. RESULTS: CYS patients have an increased prevalence of atopic disease compared to disease controls (p = 0.03) and 16.7% of CYS subjects were diagnosed with allergic disease to a variety of antigens. CONCLUSION: Further studies are needed to define the relationship between proximal tubular transport defect of CYS and dysregulated immunity.

Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor.

People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood-brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.

The SGLT2 inhibitor dapagliflozin improves kidney function in glycogen storage disease XI.

Glycogen storage disease XI, also known as Fanconi-Bickel syndrome (FBS), is a rare autosomal recessive disorder caused by mutations in the SLC2A2 gene that encodes the glucose-facilitated transporter type 2 (GLUT2). Patients develop a life-threatening renal proximal tubule dysfunction for which no treatment is available apart from electrolyte replacement. To investigate the renal pathogenesis of FBS, SLC2A2 expression was ablated in mouse kidney and HK-2 proximal tubule cells. GLUT2Pax8Cre+ mice developed time-dependent glycogen accumulation in proximal tubule cells and recapitulated the renal Fanconi phenotype seen in patients. In vitro suppression of GLUT2 impaired lysosomal autophagy as shown by transcriptomic and biochemical analysis. However, this effect was reversed by exposure to a low glucose concentration, suggesting that GLUT2 facilitates the homeostasis of key cellular pathways in proximal tubule cells by preventing glucose toxicity. To investigate whether targeting proximal tubule glucose influx can limit glycogen accumulation and correct symptoms in vivo, we treated mice with the selective SGLT2 inhibitor dapagliflozin. Dapagliflozin reduced glycogen accumulation and improved metabolic acidosis and phosphaturia in the animals by normalizing the expression of Napi2a and NHE3 transporters. In addition, in a patient with FBS, dapagliflozin was safe, improved serum potassium and phosphate concentrations, and reduced glycogen content in urinary shed cells. Overall, this study provides proof of concept for dapagliflozin as a potentially suitable therapy for FBS.

Possible Effects of Uremic Toxins p-Cresol, Indoxyl Sulfate, p-Cresyl Sulfate on the Development and Progression of Colon Cancer in Patients with Chronic Renal Failure.

Chronic kidney disease (CKD) induces several systemic effects, including the accumulation and production of uremic toxins responsible for the activation of various harmful processes. Gut dysbiosis has been widely described in CKD patients, even in the early stages of the disease. The abundant discharge of urea and other waste substances into the gut favors the selection of an altered intestinal microbiota in CKD patients. The prevalence of bacteria with fermentative activity leads to the release and accumulation in the gut and in the blood of several substances, such as p-Cresol (p-C), Indoxyl Sulfate (IS) and p-Cresyl Sulfate (p-CS). Since these metabolites are normally eliminated in the urine, they tend to accumulate in the blood of CKD patients proportionally to renal impairment. P-CS, IS and p-C play a fundamental role in the activation of various pro-tumorigenic processes, such as chronic systemic inflammation, the increase in the production of free radicals and immune dysfunction. An up to two-fold increase in the incidence of colon cancer development in CKD has been reported in several studies, although the pathogenic mechanisms explaining this compelling association have not yet been described. Based on our literature review, it appears likely the hypothesis of a role of p-C, IS and p-CS in colon cancer development and progression in CKD patients.

Impact of Thyroid Cancer Treatment on Renal Function: A Relevant Issue to Be Addressed.

Thyroid cancers require complex and heterogeneous therapies with different impacts on renal function. In our systematic literature review, we analyzed several aspects: renal function assessment, the impact of radiotherapy and thyroid surgery on kidney functioning, and mechanisms of nephrotoxicity of different chemotherapy, targeted and immunologic drugs. Our study revealed that the renal impact of thyroid cancer therapy can be a limiting factor in all radiotherapy, surgery, and pharmacological approaches. It is advisable to conduct a careful nephrological follow-up imposing the application of body surface based estimated Glomerular Filtration Rate (eGFR) formulas for the purpose of an early diagnosis and treatment of renal failure, guaranteeing the therapy continuation to thyroid cancer patients.

Next-Generation Sequencing (NGS) Analysis Illustrates the Phenotypic Variability of Collagen Type IV Nephropathies.

Mutations in COL4A3-A5 cause a spectrum of glomerular disorders, including thin basement membrane nephropathy (TBMN) and Alport syndrome (AS). The wide application of next-generation sequencing (NGS) in the last few years has revealed that mutations in these genes are not limited to these clinical entities. In this study, 176 individuals with a clinical diagnosis of inherited kidney disorders underwent an NGS-based analysis to address the underlying cause; those who changed or perfected the clinical diagnosis after molecular analysis were selected. In 5 out of 83 individuals reaching a molecular diagnosis, the genetic result was unexpected: three individuals showed mutations in collagen type IV genes. These patients showed the following clinical pictures: (1) familial focal segmental glomerulosclerosis; (2) end-stage renal disease (ESRD) diagnosed incidentally in a 49-year-old man, with diffuse cortical calcifications on renal imaging; and (3) dysmorphic and asymmetric kidneys with multiple cysts and signs of tubule-interstitial defects. Genetic analysis revealed rare heterozygote/compound heterozygote COL4A4-A5 variants. Our study highlights the key role of NGS in the diagnosis of inherited renal disorders and shows the phenotype variability in patients carrying mutations in collagen type IV genes.

Urinary epidermal growth factor/monocyte chemotactic peptide 1 ratio as non-invasive predictor of Mayo clinic imaging classes in autosomal dominant polycystic kidney disease.

BACKGROUND: Age- and height-adjusted total kidney volume is currently considered the best prognosticator in patients with autosomal dominant polycystic kidney disease. We tested the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for the prediction of the Mayo Clinic Imaging Classes. METHODS: Urinary epidermal growth factor and monocyte chemotactic peptide 1 levels were measured in two independent cohorts (discovery, n = 74 and validation set, n = 177) and healthy controls (n = 59) by immunological assay. Magnetic resonance imaging parameters were used for total kidney volume calculation and the Mayo Clinic Imaging Classification defined slow (1A-1B) and fast progressors (1C-1E). Microarray and quantitative gene expression analysis were used to test epidermal growth factor and monocyte chemotactic peptide 1 gene expression. RESULTS: Baseline ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 correlated with total kidney volume adjusted for height (r = - 0.6, p < 0.001), estimated glomerular filtration rate (r = 0.69 p < 0.001), discriminated between Mayo Clinic Imaging Classes (p < 0.001), and predicted the variation of estimated glomerular filtration rate at 10 years (r = - 0.51, p < 0.001). Conditional Inference Trees identified cut-off levels of the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for slow and fast progressors at > 132 (100% slow) and < 25.76 (89% and 86% fast, according to age), with 94% sensitivity and 66% specificity (p = 6.51E-16). Further, the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 at baseline showed a positive correlation (p = 0.006, r = 0.36) with renal outcome (delta-estimated glomerular filtration rate per year, over a mean follow-up of 4.2 ± 1.2 years). Changes in the urinary epidermal growth factor and monocyte chemotactic peptide 1 were mirrored by gene expression levels in both human kidney cysts (epidermal growth factor: - 5.6-fold, fdr = 0.001; monocyte chemotactic peptide 1: 3.1-fold, fdr = 0.03) and Pkd1 knock-out mouse kidney (Egf: - 14.8-fold, fdr = 2.37E-20, Mcp1: 2.8-fold, fdr = 6.82E-15). CONCLUSION: The ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 is a non-invasive pathophysiological biomarker that can be used for clinical risk stratification in autosomal dominant polycystic kidney disease.

Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations.

Fabry Disease (FD) is a rare lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in α-galactosidase A (AGAL) enzyme activity. This leads to the accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3), in vital organs such as the kidneys, heart, and nervous system. While FD was initially considered predominantly affecting males, recent studies have uncovered that heterozygous Fabry women, carrying a single mutated GLA gene, can manifest a wide array of clinical symptoms, challenging the notion of asymptomatic carriers. The mechanisms underlying the diverse clinical manifestations in females remain not fully understood due to X-chromosome inactivation (XCI). XCI also known as "lyonization", involves the random inactivation of one of the two X chromosomes. This process is considered a potential factor influencing phenotypic variation. This review delves into the complex landscape of FD in women, discussing its genetic basis, the available biomarkers, clinical manifestations, and the potential impact of XCI on disease severity. Additionally, it highlights the challenges faced by heterozygous Fabry women, both in terms of their disease burden and interactions with healthcare professionals. Current treatment options, including enzyme replacement therapy, are discussed, along with the need for healthcare providers to be well-informed about FD in women, ultimately contributing to improved patient care and quality of life.

Diffusion tensor imaging for the study of early renal dysfunction in patients affected by bardet-biedl syndrome.

Kidney structural abnormalities are common features of Bardet-Biedl syndrome (BBS) patients that lead to a progressive decline in renal function. Magnetic resonance diffusion tensor imaging (DTI) provides useful information on renal microstructures but it has not been applied to these patients. This study investigated using DTI to detect renal abnormalities in BBS patients with no overt renal dysfunction. Ten BBS subjects with estimated glomerular filtration rates over 60 ml/min/1.73m2 and 14 individuals matched for age, gender, body mass index and renal function were subjected to high-field DTI. Fractional anisotropy (FA), and mean, radial and axial diffusivity were evaluated from renal cortex and medulla. Moreover, the corticomedullary differentiation of each DTI parameter was compared between groups. Only cortical FA statistically differed between BBS patients and controls (p = 0.033), but all the medullary DTI parameters discriminated between the two groups with lower FA (p < 0.001) and axial diffusivity (p = 0.021) and higher mean diffusivity (p = 0.043) and radial diffusivity (p < 0.001) in BBS patients compared with controls. Corticomedullary differentiation values were significantly reduced in BBS patients. Thus, DTI is a valuable tool for investigating microstructural alterations in renal disorders when kidney functionality is preserved.

The European Rare Kidney Disease Registry (ERKReg): objectives, design and initial results.

BACKGROUND: The European Rare Kidney Disease Reference Network (ERKNet) recently established ERKReg, a Web-based registry for all patients with rare kidney diseases. The main objectives of this core registry are to generate epidemiological information, identify current patient cohort for clinical research, explore diagnostic and therapeutic management practices, and monitor treatment performance and patient's outcomes. The registry has a modular design that allows to integrate comprehensive disease-specific registries as extensions to the core database. The diagnosis (Orphacode) and diagnostic information (clinical, imaging, histopathological, biochemical, immunological and genetic) are recorded. Anthropometric, kidney function, and disease-specific management and outcome items informing a set of 61 key performance indicators (KPIs) are obtained annually. Data quality is ensured by automated plausibility checks upon data entry and regular offline database checks prompting queries. Centre KPI statistics and benchmarking are calculated automatically. RESULTS: Within the first 24 months since its launch, 7607 patients were enrolled to the registry at 45 pediatric and 12 specialized adult nephrology units from 21 countries. A kidney disease diagnosis had been established in 97.1% of these patients at time of enrolment. While 199 individual disease entities were reported by Orphacode, 50% of the cohort could be classified with 11, 80% with 43 and 95% with 92 codes. Two kidney diagnoses were assigned in 6.5% of patients; 5.9% suffered from syndromic disease. Whereas glomerulopathies (54.8%) and ciliopathies including autosomal dominant polycystic kidney disease (ADPKD) (31.5%) were the predominant disease groups among adults, the pediatric disease spectrum encompassed congenital anomalies of the kidney and urinary tract (CAKUT) (33.7%), glomerulopathies (30.7%), ciliopathies (14.0%), tubulopathies (9.2%), thrombotic microangiopathies (5.6%), and metabolic nephropathies (4.1%). Genetically confirmed diagnoses were reported in 24% of all pediatric and 12% adult patients, whereas glomerulopathies had been confirmed by kidney biopsy in 80.4% adult versus 38.5% pediatric glomerulopathy cases. CONCLUSIONS: ERKReg is a rapidly growing source of epidemiological information and patient cohorts for clinical research, and an innovative tool to monitor management quality and patient outcomes.

Nephroplex: a kidney-focused NGS panel highlights the challenges of PKD1 sequencing and identifies a founder BBS4 mutation.

BACKGROUND: Genetic testing of patients with inherited kidney diseases has emerged as a tool of clinical utility by improving the patients' diagnosis, prognosis, surveillance and therapy. METHODS: The present study applied a Next Generation Sequencing (NGS)-based panel, named NephroPlex, testing 115 genes causing renal diseases, to 119 individuals, including 107 probands and 12 relatives. Thirty-five (poly)cystic and 72 non (poly)cystic individuals were enrolled. The latter subgroup of patients included Bardet-Biedl syndrome (BBS) patients, as major components. RESULTS: Disease-causing mutations were identified in 51.5 and 40% of polycystic and non-polycystic individuals, respectively. Autosomal dominant polycystic kidney disease (ADPKD) patients with truncating PKD1 variants showed a trend towards a greater slope of the age-estimated glomerular filtration rate (eGFR) regression line than patients with (i) missense variants, (ii) any PKD2 mutations and (iii) no detected mutations, according to previous findings. The analysis of BBS individuals showed a similar frequency of BBS4,9,10 and 12 mutations. Of note, all BBS4-mutated patients harbored the novel c.332+1G>GTT variant, which was absent in public databases, however, in our internal database, an additional heterozygote carrier was found. All BBS4-mutated individuals originated from the same geographical area encompassing the coastal provinces of Naples. DISCUSSION: In conclusion, these findings indicate the potential for a genetic panel to provide useful information at both clinical and epidemiological levels.

Preventive strategies for acute kidney injury in cancer patients.

Acute kidney injury (AKI) is a common complication of cancer that occurs in up to 50% of neoplastic patients during the natural history of their disease; furthermore, it has a huge impact on key outcomes such as overall prognosis, length of hospitalization and costs. AKI in cancer patients has different causes, either patient-, tumour- or treatment-related. Patient-related risk factors for AKI are the same as in the general population, whereas tumour-related risk factors are represented by compression, obstruction, direct kidney infiltration from the tumour as well by precipitation, aggregation, crystallization or misfolding of paraprotein (as in the case of multiple myeloma). Finally, treatment-related risk factors are the most common observed in clinical practice and may present also with the feature of tumour lysis syndrome or thrombotic microangiopathies. In the absence of validated biomarkers, a multidisciplinary clinical approach that incorporates adequate assessment, use of appropriate preventive measures and early intervention is essential to reduce the incidence of this life-threatening condition in cancer patients.

[Application of proteomics and metabolomics to study inherited kidney disorders: from big data to precision medicine].

The recent application of proteomics and metabolomics to clinical medicine has demonstrated their potential role in complementing genomics for a better understanding of diseases' patho-physiology. These technologies offer the clear opportunity to identify risk factors, disease-specific or stage-specific biomarkers and to predict therapeutic response. This article is an overview of the recent insights obtained by metabolomic and proteomic studies in inherited kidney disorders. Proteomics studies have allowed the definition of a detailed picture of protein composition, post-translational modifications and interactions in kidney-derived samples, improving our understanding of renal physiology, especially of tubular transport and primary cilium-related functions. Studies on patients' urine samples and experimental models of inherited kidney diseases have provided clues suggesting novel potential pathological mechanisms and biomarkers of disease, for example in polycystic kidney disease. Metabolomic-based studies have been recently applied to assess biological system disturbances caused by specific genetic mutations resulting in inherited kidney disorders. These studies have been mainly carried out on mouse and rat models of cystic and metabolic disorders (such as Fabry disease), and on patients' urine samples. They have provided a significant contribution in understanding disease pathophysiology, promoting the discovery of aberrant biochemical pathways and contributing to the development of targeted therapies.

Skin Architecture, Kidney Transplantation, and Their Relationship to Basal and Squamous Cell Carcinomas.

BACKGROUND/AIM: Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT). It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step. PATIENTS AND METHODS: We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC. RESULTS: KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria. CONCLUSION: KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.

The link between kidney disease and cancer: complications and treatment.

Acute and chronic kidney disease encompasses a complex set of diseases that can both lead to, and result from, cancer. In particular, kidney disease can arise from the use of chemotherapeutic agents. Many of the current and newly developed cancer chemotherapeutic agents are nephrotoxic and can promote kidney dysfunction, which frequently manifests during the terminal stages of cancer. Given the link between kidney disease and cancer development and treatment, the aim of this Review is to highlight the importance of multidisciplinary collaboration between oncologists and nephrologists to predict and prevent chemotherapeutic-induced nephrotoxicity. As new therapies are introduced to treat cancer, new renal toxicities require proper diagnosis and management. We anticipate that multidisciplinary collaborations will lead to the development and implementation of guidelines for clinicians to improve the therapeutic management of patients with both cancer and renal impairment.

How to assess kidney function in oncology patients.

Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs, and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and the corresponding toxicity, whereas underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. This is of utmost importance in patients with cancer. Evaluation of kidney function is not only limited to the estimation of glomerular filtration rate or creatinine clearance. An accurate assessment of kidney function is advisable to reduce variability in decision making and ultimately the therapeutic outcomes of toxicity and clinical benefit. Therefore, additional studies are needed to investigate the validity of currently used formulas estimating kidney function in this population as well as their applicability to traditional chemotherapy, novel targeted therapies, and immunotherapies. Because of rapid discovery and development of new cancer agents, a reliable and comprehensive manner to screen for potential nephrotoxicity is critically important. As kidney function not only is limited to glomerular filtration rate changes but also involves tubular and even vascular dysfunction, urinalysis and kidney imaging studies should also be considered before therapeutic decisions are taken. However, several questions remain regarding these new technologies such as kidney-on-a-chip systems for the assessment of kidney function and injury, particularly in oncology, and it has yet to be implemented in clinical practice.

The number of nephrons in different glomerular diseases.

BACKGROUND: The total number of nephrons has been measured mainly from post-mortem studies and only in selected populations. Data from living subjects are scanty, and direct comparisons among different glomerular diseases are lacking. The present work exploits modern methodology to estimate the total nephron number in glomerulopathies with prevalent proteinuria/nephrotic syndrome versus glomerulopathies with nephritic syndrome (IgA nephropathy (IgAN), lupus nephritis), thus extending previous observations about the number and function of glomeruli in different physiological and pathological states. METHODS: This is a retrospective study based on one hundred and seven patients who have undergone renal biopsy. The glomerular density has been estimated from the biopsy specimens and the total cortical volume has been obtained from ultrasound recordings. Stereological methods have been applied to calculate the total number of nephrons and their volume. The correlation between clinical parameters and quantitative morphological data have studied using the Pearson correlation coefficient (r). RESULTS: The total number of nephrons inversely correlated with the systolic blood pressure (r = -0.4, p < 0.05). In proteinuric diseases, such as focal segmental glomerulo-sclerosis (FSGS), membranous nephropathy (MN) and diabetes, the change in estimated GFR (eGFR) directly correlated with the total number of non-sclerotic glomeruli (NSG) (r = 0.62, p < 0.01), whereas in nephritic syndrome no significant correlation was observed. The alterations in eGFR occurring in nephritic syndromes such as IgAN cannot be explained on the basis of the number of NSG. DISCUSSION: The fusion of the podocyte foot-processes that typically occurs in purely proteinuric diseases does not modify the glomerular filtration rate: therefore in these situations, the change in eGFR depends mainly on the number of available glomeruli. On the other side, the eGFR decrease occurring in nephritic syndromes, such as IgAN, cannot be explained simply on the basis of the number of NSG and likely depends on the substantial involvement of the mesangial axis. Future studies should verify whether these changes are reversible with appropriate therapy, thus reversing eGFR decrease.

Summary of the International Conference on Onco-Nephrology: an emerging field in medicine.

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

[The unusual couple: a clinical case of coexistence between aHUS and Fabry's disease].

Atypical hemolytic-uremic syndrome (aHUS) is a rare, potentially lethal (1-4) systemic disorder, capable of affecting both adults and children, causing thrombotic microangiopathy (TMA) (5) that leads to the formation of thrombus within small blood vessels with multiple organ failure. The pathogenesis of the aHUS is part of a sort of chronic and uncontrolled activation of the complement system by genetic mutation of some proteins usually responsible for its self-regulation (6,7). Today, the rapid diagnosis of the disease and the timely start of treatment with eculizumab, improve outcomes of renal failure, stroke and heart attack (8-10). Fabry disease is a rare tesaurismosis, X linked, due to the deficiency of the lysosomal enzyme alpha-galactosidase A (11-13), necessary for the physiological catabolism of glycosphingolipids. Multisystem clinical manifestations lead to a serious degenerative pathology. The diagnostic suspicion based on anamnesis and careful research of the symptoms and then confirmed by the enzymatic dosage of alpha galactosidase or by molecular analysis, allows the early treatment of the patient with enzyme replacement therapy, guaranteeing the resolution and/or slowing down the evolution of the disease, especially in the brain, heart and kidneys. In this report, we describe the clinical case of a patient who is a carrier of both rare diseases.