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Primary hyperoxalurias (PH) are autosomal recessive metabolic disorders, characterised by overproduction and urinary excretion of oxalate, presenting with nephrolithiasis, nephrocalcinosis and kidney failure. Plasma oxalate is higher than normal in PH, and it rises further in renal failure. When glomerular filtration rate falls below 30 mL/min /1.73m2, oxalate levels increase sharply and plasma becomes supersaturated with calcium oxalate, which precipitates in body tissues (systemic oxalosis). Three types of PH are described; the most frequent is PH1 (70-80%), due to deficiency of L-alanine:glyoxylate aminotransferase (AGT), the enzyme which catalyses in hepatocytes the transamination of alanine and glyoxylate to pyruvate and glycine. That leads to accumulation of glyoxylate, which is converted both in oxalate (by lactate dehydrogenase, LDH) and glycolate (by glyoxylate reductase). Increased levels of glycolate, both in serum and urine, are the hallmark of PH1. PH2 is due to variants of gene encoding for the enzyme glyoxylate and hydroxypyruvate reductase (GRHPR), which converts both glyoxylate to glycolate and hydroxypiruvate to D-glycerate in many tissues. Pathologic variants of GRHPR gene induce increased levels of glyoxylate and hydroxypyruvate, converted by LDH to oxalate and L-glycerate respectively. High levels of glycerate, both in serum and urine, allow the metabolic diagnosis of PH2. PH3 is due to variants of HOGA gene, which catalyses the cleavage of 4-hydroxy-2- oxoglutarate (HOG) to pyruvate and glyoxylate. Increased levels of both HOG and 4-hydroxy glutamate are metabolic hallmark of PH3. In this paper, an overview of oxalate metabolism was reported, and the main features of the pathophysiology, diagnosis, clinical course and treatment of PH as well. [ABSTRACT FROM AUTHOR]

Kidney cancer is one of the most common cancers globally, ranking 9th and 14th among men and women, respectively. Advances in diagnostic techniques have enabled earlier and potentially less invasive interventions, however, this progress poses a challenge in managing low-malignancy tumors that were previously undiagnosed. To navigate treatment pathways, a deep understanding of the bidirectional relationship between Chronic Kidney Disease (CKD) and Renal Cell Carcinoma (RCC) is essential, influenced by risk factors such as hypertension and obesity. The debate between partial (PN) and radical nephrectomy (RN) continues to be fueled by a rich body of studies in the last two decades, aiming to determine the precise benefits of renal function preservation and overall survival. However, long-term monitoring remains inadequate. There is an urgent need for heightened clinical vigilance, urging meticulous periodic evaluations that include both eGFR and the urinary albumin-creatinine ratio, to identify potential deteriorations early. Furthermore, non-neoplastic renal parenchyma requires equal attention, often overshadowed by the assessment of tumor mass. A nuanced analysis is necessary to identify a range of nephropathies that guide more effective therapeutic strategies. A collaborative strategy that brings nephrologists, urologists, nuclear radiologists, oncologists, and pathologists together on a unified platform, focusing on a personalized medicine approach grounded on a profound analysis of individual risk factors, is pivotal in shaping the future of management and prevention strategies. This approach ensures a detailed therapeutic outlook and facilitates early interventions, marrying vigilance with interdisciplinary cooperation, thereby guarding against late diagnoses and offering patients a robust shield in their battle against kidney afflictions., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

A deadly embrace occurs between cancer and chronic kidney disease. The estimation of kidney function in cancer patients is of utmost interest due to its direct impact on chemotherapy dosing, selection, and eligibility for chemotherapeutics. Overestimating kidney function (determined as estimated glomerular filtration rate -eGFR) can lead to overdosing and drug toxicity, while underestimating kidney function can prevent patients from receiving novel therapies. Notably, the current measures of eGFR are not validated in transplanted patients yet. The field of onconephrology ranges from nephrotoxicity of existing and novel therapeutics, paraproteinemias, and cancer-associated electrolyte imbalance, fluid and acid-base disturbances, the effects of the destruction of cancer cells, and acute and/or chronic kidney injuries. Recently, the therapeutic armamentarium has been enriched with new agents that interfere with specific proteins involved in oncogenesis. These are the so-called target therapies, which although acquired as "targeted" therapies do not have absolute specificity and selectivity and tend to inhibit multiple targets, often involving the kidney. Renal biopsy may be critical in managing these adverse effects. Moreover, primary hematological and oncological disorders can have significant kidney implications in the form of glomerular or nonglomerular diseases presenting with proteinuria, hematuria, hypertension, and kidney function decline, specifically including cast nephropathy or systemic light chain amyloidosis, and paraneoplastic glomerulopathies that occur as a result of occult malignancy, such as Membranous Nephropathy and Minimal Change disease., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Serum creatinine concentration is an unreliable and insensitive marker of chronic kidney disease (CKD). To improve CKD detection, many European and North American laboratories and all Australasian laboratories calculate and report an estimated glomerular filtration rate (eGFR) using the Modification of Diet in RenalDisease(MDRD) formula with every request for serum creatinine concentration. The aim of this paper is to provide timely information to Clinical Chemists about the strengths, weaknesses and available evidence for the role of automated laboratory reporting of eGFR in CKD detection. The accuracy and precision of eGFRs is reasonable in most adults in whom calculated values are < 60mL/min/1.73m2. However, eGFRs should be interpreted with caution in some settings, (particularly patients with eGFRs > 60mL/min/1.73 m2 and children). This paper also discusses eGFR-related decision points for clinical actions, the indications for nephrologist referral, the importance of creatinine assays tandardisation and the role of eGFR in drug dose decision-making. In conclusion, automatic laboratory reporting of eGFR will enhance early detection of CKD, allow the timely institution of appropriate reno-and cardioprotective therapies, and better in form decisions regarding the prescription of renally excreted medications. [ABSTRACT FROM AUTHOR]

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Introduction and aims: Stages 4 and 5 of chronic kidney disease (CKD) have always been considered hard to modify in their speed and evolution. We retrospectively evaluated our CKD stage 5 patients (from 01/1/2016 to 12/31/2018), with a view to analyzing their kidney function evolution. Material and Methods: We included only patients with longer than 6 months follow-up and at least 4 clinical-laboratory controls that included measured Creatinine Clearance (ClCr) and estimated GFR with CKD-EPI (eGFR). We evaluated: the agreement between ClCr and eGFR through Bland-Altman analysis; progression rate, classified as fast (eGFR loss >5ml/min/year), slow (eGFR loss 1-5 ml/min/year) and non-progressive (eGFR loss <1 ml/min/year or eGFR increase). We also evaluated which clinical-laboratory parameters (diabetes, blood pressure control, use of ACEi/ARBs, ischemic myocardiopathy, peripheral obliterant arteriopathy (POA), proteinuria, hemoglobin, uric acid, PTH, phosphorus) were associated to the different eGFR progression classes by means of bivariate regression and multinomial multiple regression model. Results: Measured CrCl and eGFR where often in agreement, especially for GFR values <12ml/min. The average slope of eGFR was -3.05 ±3.68 ml/min/1.73 m2/year. The progression of kidney function was fast in 17% of the patients, slow in 57.6%, non-progressive in 25.4%. At the bivariate analysis, a fast progression was associated with poor blood pressure control (p=0.038) and ACEi/ARBs use (p=0.043). In the multivariable model, only peripheral obliterative arteriopathy proved associated to an increased risk of fast progression of eGFR (relative risk ratio=5.97). Discussion: Less than one fifth of our patients presented a fast GFR loss (>5 ml/min/year). The vast majority showed a slow progression, stabilisation or even an improvement. Despite the limits due to the small sample size, the data has encouraged us not to consider CKD stage 5 as an inexorable and short journey towards artificial replacement therapy., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Chronic kidney disease (CKD) is a progressively chronic disease that carries a high burden of morbidity and mortality and is associated with significant healthcare utilization and costs. Recent trends shown that the prevalence of CKD is stable in Europe and USA, whereas tends to decline in some countries with a high standard of care. According to international guidelines, chronic kidney disease (CKD) is defined as the presence of kidney damage or a glomerular filtration rate (eGFR) less than 60 ml/min. This staging method has a main drawback, its imprecise assessment of renal function at the extremes of the age bracket: the use of a fixed threshold value (glomerular filtration rate [GFR <60 ml /min]) to define chronic renal failure appears an imprecise measure in the young and in the elderly. In these two groups, in fact, the measurement of GFR is difficult to categorize in a "rigid" system of classification. The reduction of the GFR with aging is due to a complex process that leads to a steady reduction of the functioning nephrons over 40 years of age. Taken together, these findings should spur us to adopt a new definition of CKD. An age-adapted definition of CKD could be a good solution to avoid a diagnosis of CKD in elderly patients (GFR >45 ml/min) when there are no prognostic implications on survival. The adoption of this new definition would also reduce the high prevalence of the disease in the general population, with a beneficial reduction of the costs associated with monitoring a mildly decreased eGFR., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent monogenic kidney disease, alone responsible for over 10% of patients with end-stage renal disease, and with an important impact on public health. Tolvaptan (TOLV) has recently been approved in many European countries for its ability to slow disease progression in patients that are eligible for treatment. Nevertheless, the doctor's choice to prescribe the drug and the patient's compliance are strongly influenced by the aquaretic effect complications. In a cohort of patients pertaining to the Nephrology clinic of the AOU Federico II of Naples and treated with TOLV, we assessed not only the adherence to the treatment and the safety of the drug, but also the real feasibility of this therapy through specific questionnaires on sleep quality, abdominal-renal pain, quality of life and patients' general satisfaction. Within the limits of preliminary data and on the basis of the responses of our population, followed for a period of at least one year and administered the maximum titration dosage, it can be asserted that the doubts regarding the real compliance of the patients can be overcome., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Administrative databases contain precious information that can support the identification of specific pathologies. Specifically, chronic kidney disease (CKD) patients could be identified using hospital discharge records (HDR); these should contain information on the CKD stage using subcategories of the ICD9-CM classification's 585 code (subcategories can be expressed just by adding a fourth digit to this code). To verify the accuracy of HDR data regarding the coding of CKD collected in the Italian region Emilia-Romagna, we analyzed the HDR records of patients enrolled in the PIRP project, which could easily be matched with eGFR data obtained through laboratory examinations. The PIRP database was used as the gold standard because it contains data on CKD patients followed up since 2004 in thirteen regional nephrology units and includes data obtained from reliable and homogeneous laboratory measurement. All HDR of PIRP patients enrolled between 2009 and 2017 were retrieved and matched with available laboratory data on eGFR, collected within 15 days before or after discharge. We analyzed 4.168 HDR, which were classified as: a) unreported CKD (n=1.848, 44.3%); b) unspecified CKD, when code 585.9 (CKD, not specified) or 586 was used (n=446, 10.7%); c) wrong CKD (n=833, 20.0%); d) correct CKD (n=1041, 25.0%). We noticed the proportion of unreported CKD growing from 32.9% in 2009 to 56.6% in 2017, and the correspondent proportion of correct CKDs decreasing from 25.4% to 22.3%. Across disciplines, Nephrology showed the highest concordance (69.1%) between the CKD stage specified in the HDRs and the stage reported in the matched laboratory exam, while none of the other disciplines, except for Geriatrics, reached 20% concordance. When the CKD stage was incorrectly coded, it was generally underestimated; among HDRs with unreported or unspecified CKD at least half of the discharges were matched with lab exams reporting CKD in stage 4 or 5. We found that the quality of CKD stage coding in the HDR record database was very poor, and insufficient to identify CKD patients unknown to nephrologists. Moreover, the growing proportion of unreported CKD could have an adverse effect on patients' timely referral to a nephrologist, since general practitioners might remain unaware of their patients' illness. Actions aimed at improving the training of the operators in charge of HDRs compilation and, most of all, at allowing the exploitation of the informative potential of HDRs for epidemiological research are thus needed., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Osteoporosis affects a segment of the population in which Chronic Kidney Disease is also greatly represented. Nephropathic patients may present peculiar biochemical abnormalities related to Chronic Kidney Disease, defining the Mineral and Bone Disorder. This kind of anomalies, in the worst scenarios, configure the typical histomorphology patterns of Renal Osteodystrophy. Scientific Societies of Endocrinology have established therapy guidelines for patients with osteoporosis only based on the glomerular filtration rate and recommend avoiding the use of some drugs for the more advanced classes of nephropathy. However, there is no clear therapeutic approach for patients with advanced nephropathy and bone abnormalities. In this paper we propose a systematic review of the literature and present our proposal for managing patients with advanced nephropathy, based on eGFR and on presence of Mineral and Bone Disorder., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Kidney transplant from donor after circulatory death (DCD) represents a valid choice to increase the incidence of renal transplantation, presenting recipients' and grafts' survival rates comparable to those from brain dead donors (DBD). In January 2016, the Transplant Referral Center in the Emilia Romagna region has started a DCD program. In the present study we report on the first 30 months of the program as far as our own Center in Bologna is concerned, and we provide a comparison with DBD transplants performed over the same period. From January 2016 to September 2018, 16 kidney transplants from 10 DCD donors (5 SCD-DCD and 5 ECD-DCD) have been performed, with two graft-loss at 12 months of follow-up, both due to renal artery rupture caused by infectious arteritis with consequent transplantectomy. Two patients died due to sepsis. Seven (44%) delay graft function (DGF) have been reported. No differences have been found between DCD and DBD in terms of kidney function (serum creatinine and eGFR evaluated at discharge, 12 and 24 months of follow-up). Kidney from marginal donors (ECD-DCD or KDPI >65%) were associated with a higher rate of DGF and worst graft function at discharge. All the predicting factors that have been analysed, including Karpinsky Score, failed to show an association with serum creatinine and eGFR at 12 and 24 months of follow up., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Acute renal injury (AKI) occurs in 19% of patients with sepsis, 23% of those with severe sepsis and up to 50% of patients with septic shock. AKI represents an independent prognostic factor of mortality (about 45%); epidemiological studies have pointed out that the onset of AKI in sepsis (S-AKI) correlates with an unfavourable outcome, reaching a mortality of 75%. Over the years, efforts have been made to prevent and treat "low flow" hemodynamic damage resulting from shock by increasing renal blood flow, improving cardiac output and perfusion pressure. New experimental studies in S-AKI have shown that renal blood flow is maintained, and indeed increases, in the course of septic shock. Recently, a "single theory" has been proposed that defines acute renal injury as the final result of the interaction between inflammation, oxidative stress, apoptosis, microcirculatory dysfunction and the adaptive response of tubular epithelial cells to the septic insult. The type of treatment, the dose and the starting time of RRT are of strategic importance in the recovery of AKI in septic patients. The use of new anticoagulation strategies in critically ill patients with S-AKI has allowed treatments to be carried out for enough time to reach the correct dose of purification prescribed, minimizing down-time and bleeding risk. The availability of new technologies allows to customize treatments more and more; the collaboration between nephrologists and intensivists must always increase in order to implement modern precision medicine in critical care., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

The management of acute kidney injury in the critical area is complex and necessarily multidisciplinary, but the nephrologist should maintain a pivotal role, both in terms of diagnosis and of indication, prescription and management of extracorporeal replacement therapy. The most frequent causes of AKI in the critically ill patients are correlated to sepsis and major surgery, but the incidence of different causes, of strict nephrological relevance, is probably higher than the estimate. Nephrologists have the competence to evaluate data relating to renal functions, urinary electrolytes, urinary sediment, and to identify which specific examinations can be useful to define the cause of AKI. A nephrological consultation will therefore improve the clinical management of AKI by guiding and integrating the diagnostic path with traditional or more advanced assessments, useful for the identification of the different causes of acute kidney damage and consequently of the most appropriate therapy. The etiological diagnosis of AKI will also be crucial in defining the renal prognosis and therefore an appropriate nephrological follow up., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Changes in microbiology and dialysis techniques in intensive care have made the use of antibiotics on nephropathic patients more complex. Several recent studies have modified our knowledge about the use of antibiotics in the care of critically ill patients, highlighting the frequency of their inappropriate use: both underdosing, risking low efficacy, and overdosing, with an increase in toxicity. Kidneys, organs devoted to excretion and metabolism, are a potential target of pharmacological toxicity. Extracorporeal replacement therapy is also a possible drug elimination route. What we call nefropharmacology represents a complex, tangled and rapidly evolving subject of multi-specialist interest. We have reviewed here most of the recent literature dealing with the appropriateness of antibiotic use, focusing on the most interesting contributions from a nephrological perspective., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

After a quick description of the anatomopathology and physiopathology of renal failure, the Authors delve into the problem of assessing its medicolegal aspects in the fields of civil invalidity and social security. In Italy, civil invalidity involves protecting the psychological and physical welfare of the disabled, as sanctioned by law 118 of 1971; this law protects all citizens with a debilitating condition, including those who do not work or are not of working age. A disabled person is someone who, if of working age (between 18 and retirement) has a reduction of more than ⅓ (34%) of their general work capacity; if under or over the retirement age, they have a persistent difficulty in carrying out age-appropriate functions and tasks. In support of an application for being awarded civil invalidity, people can also refer to law no. 104 of 1992, which assesses social, relational and work disadvantages of a disabled person. INPS (Italian Social Security Institute) protection, on the other hand, is a social security protection based on health requirements (having a capacity for work which is reduced by more than ⅓, as established by law no. 222 of 1984), as well as on the following administrative requirement: having paid, as a worker, at least 260 weekly contributions, equivalent to five years of contribution and insurance, of which 156, equal to three years of contribution and insurance, were made in the five-year period preceding the date of submitting the application. If this is the case, the protected person, thus insured, can enjoy protection for their illness by virtue of the stipulations for social security., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

The PIRP project was conceived in 2004; with the aim to face the increased prevalence of chronic kidney disease (CKD) associated with the aging and increased survival of the population. The first phase of the project consisted of training primary care physicians to identify people at risk of CKD and to implement intervention strategies that proved to be effective in preventing CKD it or delaying its progression once it is established. In the second phase of the project, dedicated ambulatories were opened in the nephrology units of Emilia-Romagna hospitals to provide an in-depth assessment and personalized care to CKD patients, following them up until renal failure or death or referring them back to general practitioners, according to the study protocol. A web-based registry was implemented to collect demographic and clinical data on PIRP patients. As of 30 June 2018, the registry included 26.211 CKD patients, with a median follow-up of 24.5 months. Over the 14 years of the PIRP the mean age of incident patients increased from 71.0 years to 74.2 years and the mean eGFR increased from 30.56 to 36.52 mL/min/1.73 m ², proving that the project was successful in recruiting older patients with a better renal function. At 5 years, the percentage of patients still active in the project was =45%.The implementation of the project has seen a reduction in the number of patients arriving every year to the dialysis treatment in E-R (about 100 units less from 2006 to 2016). The PIRP cohort is the largest in Italy and in Europe, which makes it ideal for research based on international comparisons and as a model for national registries., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

With the aging of the population, the prevalence of chronic kidney disease (CKD) is increased. Measurement of glomerular filtration rate as a screening tool may over-diagnose CKD, especially when proteinuria is normal, but it can be very useful when considering drug metabolism. Renal dysfunction is a factor predisposing to potential adverse drug reactions, because drug can accumulate to toxic levels. In addition, some drugs are nephrotoxic and can more easily damage the kidneys in the elderly. Limited data are available on the risks of drugs in the elderly population with CKD. Drugs with no clear evidence-based indication, drugs with higher risks of adverse side effects compared to their benefits, and drugs which are not cost-effective, have been defined "potentially inappropriate medications" (PIMs). Even if criteria to evaluate PIMs and adverse drug reactions are available to clinical management, we strongly support the idea that the issue of PIMs in the elderly affected by CKD should be better studied and defined. The Italian website Slow Medicine, based on the US project "Choosing Wisely", opened a new strategy in this field, taking into consideration both economic issues and patients quality of life. The main goal of this initiative is avoiding wasteful or unnecessary medical tests, treatments and procedures.

The early phases of diabetic nephropathy are characterized by an increase of GFR that, according to the tubular hypothesis, is secondary to alterations of proximal tubules. Experimental studies have in fact shown that hyperglycemia induces an increase in proximal re-absorption due to hypertrophy of tubular cells with consequent increment of sodium-glucose co-transport. The increased re-absorption in turn causes a reduction of the distal delivery of solutes and, through activation of tubuloglomerular feedback, an increase in single- nephron GFR. The resulting hyper-filtration has been proposed as a main risk factor for progression of diabetic renal disease. Limiting this early alteration may therefore represent a useful strategy for the prevention of diabetic nephropathy, that represents the major cause of ESRD in the western world today. Dapagliflozin, a competitive and highly selective inhibitor of sodium-glucose co-transport, reduces proximal tubular glucose re-absorption, increases renal glucose excretion, and reduces hyperglycemia in a dose-dependent manner. This singular mechanism of action may also have a limiting effect on diabetic hyper-filtration. Clinical trials are therefore warranted to evaluate the reno-protective efficacy of this drug in the long term.

Introduction: The term 'kidney dysfunction' is increasingly used in cardiological literature to indicate different forms of impaired kidney function which can usually be grouped within the broad categories of Acute Kidney Injury (AKI) or Chronic Kidney Disease (CKD)., Methods: In this review, renal function parameters commonly utilized in patients with acutely decompensated heart failure are illustrated. Some concepts of definition and classification of renal dysfunction in this clinical setting are presented, on the basis of the most recent data in the literature. Aspects of epidemiology and limits of methodologies are explored, in addition to the correct interpretation of findings, and the impact and prognostic value of renal dysfunction within the context of heart failure will be discussed., Results: An impairment of kidney function is frequently observed in patients with heart failure, especially during the acutely decompensated phase (Acutely Decompensated Heart Failure or ADHF). Importantly, this complication may impact negatively on clinical outcomes, as well as directly affecting the choice of therapeutic approach, especially when congestive cardiac failure is present. New, recently proposed bio-markers are indicative of kidney injury and cannot be used to replace classical functional indexes., Conclusion: The evaluation of kidney function, together with the correct interpretation of the significance of clinical findings and the limitations of specific laboratory results, bears major methodological relevance for the care of patients with heart failure. At the present time, more extensive utilization of the new kidney injury bio-markers cannot be recommended in the care of patients with acute decompensated heart failure.

Introduction: Anderson-Fabry disease (AFD) is a multiorgan X-linked lysosomal storage disease that particularly affects the heart, kidneys, and cerebrovascular system. Current treatment is with enzyme replacement therapy (ERT), using either beta-galactosidase ('Fabrazyme') or alpha-galactosidase ('Replagal'). From June 2009, it was recommended that patients switch to alpha-galactosidase due to a manufacturing shortage of beta-galactosidase. This study assesses the effect of switching to alpha-galactosidase on clinical outcomes in patients with AFD previously treated with beta-galactosidase., Patients and Methods: Ten patients (seven male, three female) with genetically confirmed AFD and at least 48 months continuous data collected during treatment with beta-galactosidase 1 mg/kg every other week, were switched to alpha-galactosidase 0.2 mg/kg every other week for at least 20 months, with prospective clinical evaluations performed every 6 months. Pre-switch data was collected retrospectively from patient charts. Cardiac functional parameters were assessed using magnetic resonance imaging., Results: Results showed that renal function generally remained stable after the switch. Cardiac mass had already decreased significantly (p < 0.05 vs pre-ERT) after introduction of beta-galactosidase and remained unchanged after switching to alpha-galactosidase. Symptoms of pain and health status scores did not deteriorate during alpha-galactosidase therapy. Adverse events were mostly mild and infusion -related., Discussion: In conclusion, switching to alpha-galactosidse was generally well tolerated and associated with stable clinical status and preservation of both renal and cardiac function.

Relation studies between bone and immune system converge in recent years in osteoimmunology chapter. It has been suggested that prostate cancer cells may alter bone homeostasis, renal function and the immune system. The aim of this paper is to evaluate bone metabolism, renal function and immune process in prostate cancer patients versus control. Patients with prostate malignancy and bone metastases showed a condition of hypocalcemia and hypophosphatemia associated with increased bone anabolism and lymphopenia, suggesting a possible correlation between bone metabolism and immune context in prostate cancer.

The last few years have seen a steady rise in numbers of patients with chronic kidney disease (CKD), mainly because of the increased prevalence of older patients. Today, most new diagnoses of CKD are made in patients belonging to the large subgroup of subjects aged 65 years or over, who often present with mild-to-moderate CKD. Given the recent rise in numbers of elderly CKD patients referred to American renal clinics, the American Society of Nephrology has recently endorsed a study group dedicated to this group of patients, Geriatric Nephrology, with the aim of increasing knowledge on CKD in the elderly and subsequently improving the clinical management of older patients. Indeed, several questions remain open and further studies are required to clarify diagnostic criteria for 'true' CKD in the elderly and the associated 'real' clinical implications in terms of hard outcomes. This review aims to address a hot topic through evaluation of the most recent and influential studies regarding the relationship between ageing and CKD.

Cardiorenal syndrome is a pathophysiological heart and kidney disorder, in which acute or chronic dysfunction of one organ induces a damage in the other. It's a syndrome more and more often encountered in clinical practice and this implies the need to recognize the syndrome through biochemical markers with a good sensitivity and specificity, since its earliest stages in order to optimize therapy. In addition to widely validated biomarkers, such as BNP, pro BNP, creatinine, GFR and cystatin C, other promising molecules are available, like NGAL (neutrophil gelatinase-associated lipocalin, KIM-1 (kidney injury molecule-1), MCP-1 (monocyte chemotactic peptide), Netrin-1, interleuchin 18 and NAG (N-acetyl-β-glucosa-minidase). The role of these emerging biomarkers is still not completely clarified: hence the need of new clinical trials.

The recent IDEAL (Initiating Dialysis Early and Late) study showed that uremic symptoms generally start when MDRD eGFR is >6 mL/min and that it is safe to delay dialysis until symptoms or biochemical evidence of uremia develop as long as the patient is already prepared for dialysis and there is adequate supervision. The results of the study support the existing guidelines and raise new questions to be answered in new trials. Francesco Casino proposes a new approach to dialysis initiation (the ''incremental approach'') whereby the dialysis dose is gradually increased as the GFR declines. Chiara Venturelli and Giuliano Brunori, on the basis of a relatively small clinical trial in the elderly (very close clinical supervision and very low protein diet supplemented with keto analogues) suggest that the start of dialysis may be delayed also to a stage where the GFR is less than 5 mL/min. Both these intriguing proposals should be considered as a rational basis for new studies rather than as recommendations for clinical practice.

In the past, the initiation of dialysis treatment was determined by the appearance of signs and symptoms of uremia along with biochemical parameters. More recently, based on the findings of observational studies, it was hypothesized that an earlier start would benefit patients. The endorsement of this concept by international guidelines has led to the current practice of starting dialysis at GFR levels of 10 to 15 mL/ min/1.73 m2. However, recent observational studies taking into proper account the lead time bias showed a worse rather than better prognosis in early starters, suggesting that the previous studies might have been flawed. The IDEAL (Initiating Dialysis Early And Late) study has shown that starting dialysis ''just in time'', i.e., at the occurrence of uremic symptoms, does not harm the patient in that it is associated with the same clinical outcomes as early dialysis initiation. We believe that these results are compatible with our hypothesis that starting peritoneal dialysis or hemodialysis with an incremental modality could be appropriate for an asymptomatic patient with objective signs of mild uremia and a measured GFR around 10 mL/min/1.73 m2. In fact, when the GFR is relatively high, a reduced dialysis dose and/or frequency could suffice to control mild uremia, while possibly preserving the residual renal function owing to the reduced contact time between blood and bio-incompatible dialysis materials. The dialysis dose and/or frequency could be increased step by step, at the occurrence of symptoms, marked biochemical derangements or problems with volume control, without computing weekly Kt/Vurea.

Current recommendations for the initiation of dialysis are based on the level of kidney failure and on clinical evidence of uremia. Several nephrology societies advocate the early start of dialysis, i.e., when the glomerular filtration rate (GFR) is higher than or equal to 10 mL/min/1.73 m2, to minimize the clinical and social problems related to advanced uremia. It is not fully known whether the early start of dialysis is beneficial, harmful or neutral with respect to the outcome of dialysis treatment in end stage renal disease. Recent studies have reported no benefit in patient survival from initiating dialysis treatment at a higher GFR. The available data indicate that the mortality while on dialysis may be higher with an early start, and that there is no significant benefit in terms of quality of life. Whether this is explained by a greater comorbidity burden or detrimental effects of early initiation remains unclear. In clinical practice, there is considerable variation in the timing of initiation of maintenance dialysis for patients with end stage renal disease. We support initiating dialysis at a lower GFR (< -7.0 mL/min) provided that patients are given careful clinical management, and at an even lower rate in selected elderly patients given a supplemented very low protein diet. In this group of patients it is possible to initiate dialysis at a very low GFR (< -5 mL/min/1.73 m2) if there is careful management of the nutritional status, fluid and electrolyte balance, body weight, mineral metabolism, anemia, and blood pressure.

It is still a matter of debate whether peritoneal dialysis should be initiated with a full dose regimen or with incremental doses. The use of low-dose dialysis is not always feasible, but it may have the advantages of improved quality of life and lower infective and metabolic complication rates. However, incremental peritoneal dialysis has to meet the minimal suggested adequacy targets in terms of depuration (Kt/V, creatinine clearance), ultrafiltration, and electrolyte balance. Incremental peritoneal dialysis has been proved feasible and safe in asymptomatic patients with a glomerular filtration rate (GFR)<6 mL/min, but the residual renal function has to be monitored strictly. A second population is composed of asymptomatic, mostly older patients with GFR between 6 and 10 mL/min, in whom a low-dose start may preserve the residual renal function and favor a more gradual training. Lastly, patients with severe, terminal, chronic cardiomyopathy who are not candidates for a heart transplant may experience beneficial effects on cardiac function and hospitalization with low-dose peritoneal dialysis treatment even when they have GFR>10 mL/min. In conclusion, incremental peritoneal dialysis is a feasible therapeutic option that the nephrologist should know and be able to perform in those patients who may benefit from it.

Background: Controlled clinical trials have defined the characteristics of specialized world populations, different from the real world population. On this basis, the GIPSI registry was created, aiming to collect data from heart failure populations managed by general practitioners, focusing on gender differences., Methods: The registry was based on family history, clinical and laboratory data collection from general practitioners. Patients were considered as being at risk for heart failure if data applied to stage A/B, or presenting overt heart failure if data applied to stage C/D of the American College of Cardiology/American Heart Association classification., Results: From June 2006 to October 2007, 757 consecutive patients (475 male, 62.7%) were enrolled from 260 general practitioner's practices; 227 patients (143 male, 63.0%) had overt heart failure. In the female population at risk, higher systolic and diastolic blood pressure values were observed, whereas males showed more frequently ischemic heart disease, hypercholesterolemia and hypertriglyceridemia, and were more often prescribed with statins and antiplatelet drugs. There were more heart failure females with diabetes and of advanced age. Moreover, females showed a higher pulse pressure and a significantly lower estimated glomerular filtration rate (by simplified MDRD equation) than males., Conclusions: The data collected in a real world population show that heart failure has significantly different gender characteristics, especially for risk factors, age, blood pressure and renal function. This kind of investigation should be extended to larger patient populations for a better understanding of the disease.

Current guidelines suggest to evaluate kidney function by estimates of the glomerular filtration rate (GFR) calculated using the Cockcroft-Gault equation or the simplified equation of the Modification of Diet in Renal Disease (MDRD) study. Cockcroft and Gault developed a method to predict an individual's creatinine clearance without urinary data but on the basis of average creatinine clearance values corrected for age and body weight. The equation needs information about gender, age, weight, and serum creatinine. The precision of the equation is biased by overweight because the equation is based on the assumption that creatinine clearance linearly reflects body weight. The MDRD equation derives from a multiple regression used to analyze the relation of GFR measurements by a radioisotope technique over serum creatinine after data linearization by logarithm transformation and with control for gender, age, ethnicity and other variables. The equation has not been validated for GFR >60 mL/min x 1.73 m2 because the study did not include healthy persons. The two equations often give conflicting estimates of GFR. Nephrologists have to understand the rationale of the two equations for the correct interpretation of these discrepancies.

Purpose: The aim of this paper is to report on the implementation of new guidelines on the use of injectable iodinated contrast media (ICM) at our workplace and specific protocols for the preparation of patients at risk., Materials and Methods: Operators received training with continuing medical education (CME) credits. The new documentation (patient history/screening form and informed consent form) is available on the hospital Web site and requests serum creatinine determination with estimation of glomerular filtration rate (GFR) for every patient. Additional tests are required for high-risk patients only., Results: Attendance rates were 57.2% among referring physicians and 74.5% among Radiology Department personnel. The Cockcroft-Gault formula was used to estimate GFR in adults. The main problem encountered in the implementation process was that referring physicians failed to evaluate the GFR in 80% of patients, with low GFR being discovered in the Radiology Department on the day of examination in 20% of patients, resulting in a need to reschedule the examination., Conclusions: Although not an easy task, implementation of the new guidelines for ICM use is both feasible and necessary. An additional refresher training course for personnel and GFR evaluation of the patient on referral are indispensable to ensure proper preparation of patients at increased risk of adverse reactions to ICM.

Many parameters of biological functions, interesting different branches of medicine, have to be indexed by the same value for each other comparison between single individuals or between-within groups.Body Surface Area (BSA) and 1.73 m2 reference value are probably the most used tools for indexation, but a growing number of scientific papers emphasize the risk of under or over estimates of data by BSA indexation in overweight-obese or on the contrary underweight individuals. This study has been planned to evaluate such a problem: a) by a theoretical approach, indexing to 1.73 m2 the creatinine clearance(CtCl) in an ideal population, and b) analysing and debating the doubts and problems about the indexation by BSA in many fields, the possibilities of indexation by other methods, or to use BSA with different approach, to reduce the risk of bias, evaluating the possibility of this target in a real population of 45 men and 84 women undergoing Peritoneal Dialysis (PD) - II - The feasibility to agree to an identical value of normal or abnormal renal function for every age or, on the contrary, to have a normal range for each age, are analysed and discussed.About BSA as indexing tool, it is pointed out: a) the lack of significative correlation between BSA and GFR and other parameters b) the increasing gap during years between 1.73 m2 BSA and the average BSA.

Many parameters of biological functions, interesting different branches of medicine, have to be indexed by the same value for each other comparison between single individuals or between-within groups. Body Surface Area (BSA) and 1.73 m2 reference value are probably the most used tools for indexation, but a growing number of scientific papers emphasize the risk of under or over estimates of data by BSA indexation in overweight--obese or on the contrary underweight individuals. This study has been planned to evaluate this problem: a) by a theoretical approach, indexing to 1.73 m2 the creatinine clearance (CtCl) in an ideal population and b) analysing and debating the doubts and problems about the indexation by BSA in many fields, the possibilities of indexation by other methods, or to use BSA with different approach, to reduce the risk of bias, evaluating the possibility of this target in a real population of 45 men and 84 women undergoing Peritoneal Dialysis (PD). The effects of indexing 1.73 m2, according different weights on the CtCl of the ideal population and on the values of BSA estimation according different formulae. Results, methods, and the problems due to abnormal fluctuation of weight compared to normal range of standard value according height are analyzed and discussed.

Contrast-induced nephropathy is an impairment in renal function following intravascular exposure to radiographic contrast media (CM). Kidney damage may be limited to an asymptomatic increase in serum creatinine or reveal itself as acute renal failure, which can require renal replacement therapy. The aim of the present review is to describe the most recent knowledge concerning this matter. Viscosity and/or osmolality of iodinated CM might be involved in the activation of intrarenal vasoconstriction, with a subsequent decrease in glomerular filtration rate. Reduced bioavailability of physiological vasodilators, such as prostaglandins and nitric oxide, could predispose to acute renal damage. The volemic expansion and hydration of the patient, by the peri-procedural infusion of saline solutions constitutes even today the most effective prophylactic mechanism. It is probable, in fact, that in this way the dilution of CM and the inhibition of the activation of intrarenal vasoconstrictive mechanisms are obtained.

The glomerular filtration rate is generally accepted as the best overall measure of kidney function and many scientific organizations recommend the use of equations that estimate this parameter to facilitate the diagnosis, evaluation and management of chronic kidney disease. Large-scale epidemiological studies have shown that a mild to moderate reduction in glomerular filtration rate is not an uncommon condition in the general population, and its prevalence further increases in patients at higher cardiovascular risk. Moreover, a large body of evidence has recently established that even minor renal dysfunction is an independent predictor of adverse cardiovascular prognosis. The excess cardiovascular risk related to renal damage is due in part to a higher prevalence of traditional atherosclerotic risk factors, in part to nontraditional, emerging risk factors peculiar to chronic kidney disease which enhance the atherogenic process at the systemic level. Therapeutic approaches in the presence of renal damage are aimed at providing simultaneous cardiovascular and renal protection. Optimal blood pressure control, as indicated by international guidelines, is of the utmost importance both to slow the progression of renal damage and to prevent cardiovascular events. Better outcomes of renal function can be obtained with inhibition of the renin-angiotensin system in both diabetic and nondiabetic renal disease, although the administration of a combination of antihypertensive drugs will be required in almost every patient to achieve the blood pressure target. Aggressive intervention on associated modifiable cardiovascular risk factors is also advisable in order to optimize the global risk profile of patients with chronic kidney disease.

Purpose: Magnetic resonance diffusion-weighted imaging (MR-DWI) is useful to assess proton motion by the computation of an apparent diffusion coefficient (ADC). This property could be used to assess renal damage, with special regard to unilateral dysfunction. The aim of this study was to estimate the correlation between ADC and the stage of chronic renal failure (CRF) using a spin-echo echo-planar imaging (SE-EPI) sequence with the sensitivity encoding (SENSE) technique., Materials and Methods: Fourteen patients (nine men and five women, mean age 49 years, range 22-66 years) underwent an MR examination on a 1.5-T system. Seven patients had a history of hypertension or CRF, one had Takayasu disease and one had nephrovascular hypertension. Five subjects without known kidney disease were used as controls. The glomerular filtration rate (GFR) assessed by Cockcroft-Gault's equation was used as a functional marker. The imaging protocol consisted of T1- and T2-weighted sequences followed by a SE-EPI acquisition with a diffusion gradient of 600 s/mm(2) and SENSE factor 2 and pixel-by-pixel ADC map reconstruction. In five patients, the SE-EPI-DWI sequence was repeated after i.v. administration of 1 mg of furosemide., Results: ADC was of 2.44+/-0.24 x 10(-3) mm(2)/s in patients with normal GFR and of 2.05+/-0.33 x 10(-3) mm(2)/s (p<0.05) in subjects with altered GFR; a significant difference was found between stage III and IV (p<0.01), whereas no differences were found between stage I and II (p=0.27) and between stage II and III (p=0.39). A good correlation was found between GFR and ADC (r=0.79; p<0.01), with no significant change after furosemide administration (p=0.7)., Conclusions: DWI is a feasible MR technique for assessing renal damage. Further studies with scintigraphic correlation are needed to confirm these results and to establish reference values for this imaging technique.

Background: The onset of clinical proteinuria in patients with diabetic nephropathy usually marks the existence of irreversible and progressive kidney damage. Prevention of chronic renal failure ought to take place in earlier stages, mostly in the outpatient setting and in close collaboration with general practitioners (GPs). This study aims to evaluate the prevalence and the clinical stage of diabetic nephropathy and to screen for progression factors in the regional community referred to the outpatient department of the nephrology unit of the Mons. DiMiccoli Hospital in Barletta; it is intended as the first phase of a collaborative project for the prevention of diabetic nephropathy., Methods: Our team asked for the collaboration of GPs within the geographic area referring to our outpatient department. This led to the institution of a working group aimed at interrelating primary with hospital care in the setting of nephrology. The clinical data of diabetic patients as well as their codified personal data were classified by GPs and subsequently processed by the nephrology team. The glomerular filtration rate was estimated by means of the abbreviated MDRD study equation. Finally, the cumulative prevalence of known risk factors for diabetic nephropathy progression was assessed in a subgroup of 201 diabetic patients., Results: Within the whole group of screened subjects from the regional community (21,314), the prevalence of diabetes was 3.54%, and the rates of personal and clinical features did not show any substantial differences from the ones recorded in Italy as a whole. In the subgroup of 201 diabetic patients, the cumulative frequency of progression factors for diabetic nephropathy showed a relevant percentage of subjects with clinical and laboratory features deviating from the targets proposed by current guidelines, thus justifying the adoption of specific prevention plans., Conclusions: This study shows the feasibility and the advantages of setting up a stable collaboration between hospital and primary care in order to improve the diagnosis and prevention of kidney disease. Identification of the most frequently deviant progression factors provides the primary target for the prevention of kidney damage in diabetic patients.