Showing papers in "Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia in 2008"

Prevalence of chronic kidney disease

Abstract: The prevalence of chronic kidney disease (CKD), especially the early stages, is still not exactly known. This is also true for CKD stage 3, when cardiovascular and other major complications generally appear. The NANHES data have shown a steady increase in the prevalence of CKD 3 up to 7.7% in 2004. Chronic kidney disease and renal failure are underdiagnosed all over the world. In Italy, prevalence estimates for stage 3 to 5 CKD are around 4 million yet, less than 30% of these subjects are believed to be followed at nephrology clinics. This means that in Italy for every dialyzed patient there are about 85 individuals with possibly progressive kidney disease, while fewer than five (mainly stage 4 and 5 patients) are actually followed by a nephrologist.

Prevalence of chronic kidney disease

Abstract: The prevalence of chronic kidney disease (CKD), especially the early stages, is still not exactly known. This is also true for CKD stage 3, when cardiovascular and other major complications generally appear. The NANHES data have shown a steady increase in the prevalence of CKD 3 up to 7.7% in 2004. Chronic kidney disease and renal failure are underdiagnosed all over the world. In Italy, prevalence estimates for stage 3 to 5 CKD are around 4 million yet, less than 30% of these subjects are believed to be followed at nephrology clinics. This means that in Italy for every dialyzed patient there are about 85 individuals with possibly progressive kidney disease, while fewer than five (mainly stage 4 and 5 patients) are actually followed by a nephrologist.

[Health-related quality of life in patients with chronic kidney disease].

Abstract: Assessment of quality of life in patients with different degrees of chronic kidney disease is an important issue because of its impact on clinical decisions and financial resource management in the health-care system The aim of this study was to assess whether a generic instrument like the SF-36 questionnaire is able to discriminate three different populations of patients with different degrees of renal disease (pre-ESRD, ESRD, TxR) Five hundred sixty-three patients from 12 Italian nephrology units completed the SF-36 scales by themselves The results from these samples were compared with those from the general population Univariate analysis and multivariate regression were used The generic SF-36 questionnaire proved to be a powerful instrument to discriminate populations with different degrees of chronic renal failure The quality of life of patients on dialysis is significantly worse than that of the normal population and other patients with less severe renal function impairment

[Latin-American Dialysis and Kidney Transplantation Registry: data on the treatment of end-stage renal disease in Latin America]

Abstract: Latin America, a region composed of a series of neighboring countries that share their history, Latin ancestry and language (Spanish or Portuguese), includes Mexico, Central America, the Spanish Caribbean islands, and South America. The Latin-American Dialysis and Kidney Transplantation Registry, which has been operative since 1991, collects data from 20 countries (Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Puerto Rico, Dominican Republic, Venezuela and Uruguay), where 97% of Latin Americans live. The prevalence of renal replacement therapy (RRT) has increased from 119 patients per million (pmp) in 1991 to 478.2 in 2005 (147,158 patients [57%] on chronic hemodialysis, 58,251 [23%] on peritoneal dialysis and 52,565 [20%] living with a functioning kidney graft). The incidence rate also increased from 27.8 pmp in 1992 to 167 in 2005. The increment in prevalence and incidence occurred in all Latin- American countries. The transplantation rate increased from 3,7 pmp in 1987 to 15 pmp in 2005 (7,968 kidney transplants performed this year, the cumulative number being 98,415). Access to RRT was available for every patient diagnosed with end-stage renal disease only in Argentina, Brazil, Chile, Cuba, Puerto Rico, Venezuela and Uruguay. In Latin America, the incidence and prevalence of RRT increased year by year. Only in some countries is access to RRT available to 100% of diagnosed patients. Detection and prevention programs for chronic kidney disease are needed in the region. Meanwhile, access to RRT has to be improved for everybody who needs it.

Thin glomerular basement membrane disease

Abstract: Thin glomerular basement membrane disease (TBMD) is a hereditary nephropathy characterized by thinning of the glomerular basement membrane evinced by electron microscopy and, clinically, by isolated hematuria without extrarenal manifestations. Familial aggregation is found in 50-60% of cases, with autosomal dominant transmission. TBMD is considered to belong to the type IV collagen spectrum of diseases, since heterozygous mutations of the COL4A3 or COL4A4 gene have been detected in more than 30% of patients. The disease is found in 1-2% of biopsies, but the prevalence in the general population may be higher. The differential diagnosis with Alport's syndrome may be difficult and requires accurate family investigations, immunohistochemical evaluation of type IV collagen alpha chains in renal tissue and, if appropriate, genetic studies. Progression towards chronic renal failure, although rare, has been reported in some patients, and may be related to the phenotypical variability of COL4A3/COL4A4 mutations, to a missed Alport syndrome, or to superimposed glomerular disease. Patients suffering from TBMD and affected relatives should be periodically examined for signs of disease progression and informed about the possibility of transmitting the autosomal recessive form of Alport's syndrome.

When a bubble bursts

Abstract: A 47-year-old man with a medical history of nephrolithiasis of the right kidney presented with abdominal pain at the level of the right hip. Ultrasonography showed an anechoic area with irregular contours in the lower pole of the right kidney, where a previous ultrasound scan had signalled the presence of a large cyst. Abdominal computed tomography revealed the presence of a fluid area within the lower pole of the right kidney. Subsequent ultrasonography showed progressive reduction of the anechoic area, which was associated with gradual reduction of the pain. The case was diagnosed as spontaneous rupture of a renal cyst. Renal cyst rupture is an infrequent, usually self-limiting event that may engender diagnostic dilemmas.

Nephrolithiasis in patients with intestinal diseases

Abstract: Intestinal diseases may cause the formation of urinary stones through changes in the metabolism of oxalate, calcium, and uric acid. The oxalate that is excreted into urine comes from the catabolism of ascorbic acid and some amino acids or from intestinal absorption of food oxalate. Calcium is absorbed by the gut after the stimulation of active vitamin D and is excreted by the kidney under the control of the bone/parathyroid hormone axis. Uric acid is generated by the oxidation of exogenous and endogenous purine bases, is excreted by the kidney through glomerular filtration/tubular secretion, and is soluble in alkaline urine. Several data indicate that patients with inflammatory bowel diseases are at high risk of urinary stones containing calcium-oxalate salt or uric acid. Calcium-oxalate stones are caused by colonic oxalate hyperabsorption (secondary to intestinal dysfunction) or by parenteral nutrition. Uric acid stones are typical of patients with severe diarrhea and/or intestinal neostomy, that is, in patients with hyperconcentrated acidic urine. Relationships between malabsorptive intestinal diseases and urinary stones are less well defined. Preventive countermeasures are not the same for all disorders. Hyperoxaluria should be controlled by diets with a low content of lipids and oxalate but supplemented with calcium and probiotics. The presence of hyperconcentrated acidic urine should be controlled by correct hydration and administration of citrate.

[Vascular access for dialysis in elderly: AVF versus permanent CVC].

Abstract: The type of hemodialysis vascular access (fistula, graft, catheter) employed plays an important role in the results of dialysis treatment. Moreover, different complications can affect the vascular access and interfere with the morbidity and mortality of patients. The ideal vascular access is the Cimino Brescia fistula, followed by graft. Tunnelled central venous catheters should be considered as 'second choice' because they present a higher incidence of complications, mainly due to thrombosis and infections. Finally, in elderly patients the vascular bed is frequently damaged and this may make it difficult to create a Cimino (Brescia) fistula (AVF). The use of instrumental tests, as echo-color Doppler or angiography in order to evaluate the real status of vascular bed in elderly patients can offer a great opportunity in order to find the best position where it is possible to create a fistula or graft. We suggest that a native fistula can be easily created in elderly patients and the 'second choice' access should be limited to a small proportion of patients. Although patient selection is important, even patients of 80 years or older who are considered suitable for surgical placement of access should not be denied an AVF solely because of age. Nephrologists or vascular surgeons, who create vascular access, should develop a good patient and site selection to predict which vascular access will function successfully rather than risk complications of prolonged central catheters.

Kidney diseases with chronic renal failure in the Italian renal biopsy registries

Abstract: The prevalence of chronic renal failure (CRF) at the time of kidney biopsy ranges between 5% and 37% in different renal biopsy registries. This wide variability is mainly dependent on the different definitions of CRF. In the period 1998-2006, the Triveneto Renal Biopsy Registry recorded 816 cases with CRF (defined as serum creatinine persistently > or =1.5 mg/dL), accounting for a prevalence of 27%. At the time of biopsy, the average age and glomerular filtration rate were 54 years and 41 mL/min, respectively; 70% of CRF patients are men and the prevalence of CRF increases with age. IgA nephropathy (IgAN) is the main histological form of glomerulonephritis, accounting for 23% of all cases of CRF. However, in subjects older than 65 years, membranous glomerulonephritis (MG) exceeds IgAN, thus becoming the main diagnosis in elderly patients with renal impairment. With a cutoff value for proteinuria of 3 g/day, the main diagnoses in cases with proteinuria below and above the cutoff are IgAN and MG, respectively. IgAN remains the main histological form of nephropathy throughout all levels of renal failure. These data confirm the findings of the Italian Registry of Renal Biopsies, but correspond only in part with data from other registries. The differences can to a certain extent be explained by the different criteria for the definition of renal impairment, patient selection, and differences in diagnosis among registries.

[Low-protein diet in Italy today: the conclusions of the Working Group from the Italian Society of Nephrology]

Abstract: The high estimated prevalence of chronic kidney disease (CKD) forcefully supports the need for collaboration among nephrologists, cardiologists, diabetologists and general practitioners, to reduce the cardiovascular risk of CKD patients and delay the start of dialysis. Many studies confirm that reducing the dietary intake of proteins improves uremia as well as acid-base and phosphorus disorders without exposing the CKD patient to the risk of malnutrition. The possibility of delaying renal death and the start of dialysis by almost one to two years is also recognized, thanks in part to the antiproteinuric effect of low-protein diets supplemented with keto acids and essential amino acids. Reducing the dietary protein intake delays the start of dialysis independently of the effect of renin-angiotensin system (RAS)-active antihypertensive drugs. Reduction of the dietary protein intake is indicated in patients with a glomerular filtration rate <25 mL/min (CKD stages 4 and 5). Some situations may, however, require an earlier switch to a low-protein diet, e.g., high proteinuria, renal function worsening at more than 5 mL/min/year, diabetes, and metabolic decompensation. If well designed and properly carried out, reduction of the dietary intake of proteins is not associated with low serum albumin levels or malnutrition, and does not affect patients death. Today, highly palatable, high-quality reduced protein preparations are widely available to reduce the protein intake of CKD patients.

Erectile dysfunction and quality of life in patients with chronic renal failure

Abstract: Erectile dysfunction (ED) is associated with a reduced quality of life; it represents a risk factor for the development of depression. ED may induce depression, loss of self-esteem, poor self-image, anxiety, and tension in the relationship with the partner. These emotional disturbances can create physical conditions that lead to increased difficulty in achieving an erection. Depression can deprive a person of the ability to experience many of life's pleasures. It not only affects the mind but also the body--often in unexpected ways. As a result, many men who have been diagnosed with depression find themselves suffering from another condition: ED. Sexual dysfunction is a big problem also in patients with chronic renal failure and seriously affects their quality of life. About 40% of men on dialysis suffer from ED. Many uremic patients have additional symptoms including reduction of libido and a decreased frequency of sexual intercourse. With the start of dialysis some of these symptoms may improve, without, however, returning to normal.

[Compliance with low-protein diet in patients with chronic kidney disease].

Abstract: Direct evaluation of the compliance with nutritional therapy is possible only in clinical trials while indirect methods such as self-reporting and interviews are used in clinical practice. Dietary history is the best method to evaluate nutritional habits in clinical practice; the same holds true for the compliance with low-protein diets in patients with chronic kidney disease. Other indexes to assess dietary compliance should be simple and easy to use in the clinical practice. Some of such functional and biological markers are blood urea nitrogen and serum phosphate levels (indirect markers of dietary intake), weight and body mass index (indirect markers of energy intake), and daily urinary excretion of nitrogen and sodium (indirect markers of protein and salt intake). The compliance with a low-protein diet in patients with chronic kidney disease is strongly influenced by psychosocial factors (e.g., satisfaction and comprehension), and thus by the supporting role of the physician and the dietitian, but also by the level of renal function and food characteristics. It must be pointed out that even a protein intake reduction of 0.2 g/kg/day improves blood urea nitrogen, phosphate levels, and acidosis.

[Autosomal dominant polycystic kidney disease: from genes to cilium].

Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a quite frequent monogenic hereditary disease. The incidence has been reported to range between 1:400 and 1:1000 life births. The disease is caused by a mutation of the PKD1 gene in 85% of the cases and by a mutation of the PKD2 gene in the remaining 15%. The main characteristic of this condition is the development of renal cysts. Observations regarding various cystic kidney diseases sustained by mutations of different genes are steadily converging to a common point. This unifying element is the primary cilium. The cilium, which has long been considered a mere biological oddity, has lately become the focus of intense scientific attention because it may turn out to be the key to the understanding of cystic degeneration. The cilia can be regarded as sensors projecting out of the cell. In particular in the kidney they are located in an ideal place to capture information from the tubular lumen. One of the roles the cilia may play is the reception of chemical signals. An alternative hypothesis attributes to the cilia the role of mechanosensors capable of detecting variations of the urine flux in the tubular lumen. The cilium projects itself into the lumen where it can readily capture variations in the external environment and transmit them to the cell by as yet undefined pathways. This is the still largely unexplored frontier that will provide the elements needed to understand and treat renal cystic diseases.

When to start dialysis. The predialysis patient

Abstract: The incidence and prevalence of chronic renal failure (CKD), defined according to the NFK-KDOQI guidelines as a glomerular filtration rate less than 60 mL/min/1.73 m2 or the presence of microalbuminuria, is increasing worldwide, leading to an increased risk of cardiovascular disease. There is general agreement about the importance of early referral to the nephrologist and predialysis educational programs because this strategy prevents the progression (by the use of renin-angiotensin system blockers, low-protein diet) and complications (arterial hypertension, anemia, malnutrition, osteodystrophy, acidosis) of renal disease. Predialysis education helps patients choose the renal replacement therapy modality (hemodialysis, peritoneal dialysis, transplantation) and improve their quality of life. Furthermore, adequate predialysis care allows the nephrologist to prepare the vascular access well in advance. In contrast to the wished-for practice of early referral, patients are often referred to the nephrologist when renal failure is already advanced. This is mainly due to the fact that non-nephrologists pay little attention to identifying patients at risk for renal failure or defining the degree of renal failure according to the KDOQI classification. In addition, serum creatinine alone provides no adequate estimate of renal function, and both the MDRD equation and the Cockcroft-Gault formula permit a more accurate estimation of the glomerular filtration rate (GFR). Using the MDRD equation, the KDOQI guidelines recommend referral when GFR is less than 30 mL/min/1.73 m2. Late nephrology referral is an independent risk factor for early death while on dialysis, as well as being associated with a more frequent use of temporary catheters, particularly in the elderly but also in patients receiving regular nephrology care. This underlines the importance of a multidisciplinary predialysis approach which may bring additional benefits - beyond referral to a nephrologists - including a reduced hospitalization rate and improved survival. The KDOQI guidelines recommend evaluating the benefits and risks of starting renal replacement therapy when patients reach stage 5 (estimated GFR <15 mL/min/1.73 m2), although the ideal time for replacement therapy initiation remains a matter of debate and the results of prospective clinical trials are awaited to resolve this issue.

[Glomerular filtration rate and cardiovascular risk: prognostic and therapeutic implications].

Abstract: 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.

[Treatment of lupus nephritis associated with end-stage renal disease].

Abstract: Approximately 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). In some cases with a rapidly progressive course, treatment may result in partial recovery of renal function. The choice of aggressive treatment should be balanced against the risk of enhanced morbidity due to side effects in patients with renal insufficiency; one should therefore desist from preventing ESRD at any cost. Renal replacement therapy (both hemodialysis and peritoneal dialysis) may offer lupus patients with ESRD good chances of survival. The indications for renal replacement therapy are similar to those in other uremic patients. Systemic lupus erythematosus activity may be quenched by renal replacement therapy but it may also persist, especially during the first year. Immunosuppression and corticosteroids should be stopped when possible, as lupus patients on dialysis are liable to increased morbidity consisting of infections and cardiovascular events due to side effects of therapy. The presence of antiphospholipid antibodies may favor thrombotic events. Renal transplant offers the best rehabillitation for most lupus patients with ESRD. Many studies have reported similar patient and graft survival rates in lupus and nonlupus transplant recipients. The results are better for living-donor transplants. Patients with antiphospholipid antibodies have a higher graft failure risk. Active lupus and iatrogenic side effects are risk factors for enhanced morbidity after transplant; a 6-12 washout period before transplant is advisable for these candidates. Recurrence of lupus nephritis is a rare event which usually does not compromise the outcome of the graft.

[Effects of kidney transplantation on bone: osteoporosis or other?].

Abstract: Post-transplant bone disease is a heterogeneous osteodystrophy because the effects of age, gender, persistent hyperparathyroidism, corticosteroid and calcineurin inhibitor therapy are superimposed. The decrease in bone mass is particularly prominent during the first 6 months after kidney transplantation and is associated with an increased number of fractures. Bone mineral density measurements do not predict bone histology. Bone biopsy reveals heterogeneous lesions, which differ during the early and later phases after transplant. Interestingly, the cases of osteoporosis (BV/TV <15%) are comparatively few, and biopsies in later phases show delayed mineralization as a common finding, and a generalized prevalence of osteomalacic lesions. Bone histology could be a useful tool to delineate the underlying histological alterations in such patients in order to develop adequate therapeutic strategies.

Folate metabolism dysfunction

Abstract: This review examines the history of folate, its metabolism and its relationship to drugs and diseases The scientific interest in folate has been increasing in recent years because of new findings related to its important role in many diseases like macrocytic anemia, congenital malformations, vascular thrombosis, atherosclerotic disease and cancer The fascinating puzzle of folate is analyzed and the most recent news about folate treatment in patients with chronic renal failure is reported

[Switch from Darbepoetin-alpha to Epoetin-alpha: cost and efficacy comparison for haemodialytic patients over one year follow-up in a single centre].

Abstract: Due to the increased emphasis on cost-containment, drugs must be proven not only to be safe and effective, but also to reduce costs, prior to be used in clinical practice. In the context of this saving policy, 12 clinically stable patients on hemodialysis who were administered darbepoetin-alpha (Aranesp (DARB) for at least 16 months in single weekly doses, were converted to EPO-alpha, administered 2-3 times per week. The initial dose of EPO-alpha was calculated on the basis of a dose-conversion ratio (DCR) of 200 IU EPO-alpha = 1 mcg DARB. The mean Hb value in the six months preceding the conversion was between 11 and 12 g/dL, with a monthly dose of DARB unchanged/ reduced during the last three months. During the last month of treatment with DARB, the mean Hb value of the cohort was 11.4+/-0.5 g/dL and the mean weekly dose per patient was 24 +/- 12 mcg. After two months of EPO-alpha use, the mean Hb value dropped to 10.8+/-0.7 g/dL, with a mean monthly dose per patient of 5.667+/-2.229 IU, corresponding to a DCR of 234. In order to bring the Hb values back to above 11 g/dL, doses of EPO-alpha were progressively increased up to a maximum of 10.000+/-5.461 IU per patient, corresponding to a DCR of 414. The attempt to convert 12 hemodialysis patients treated with darbepoetin-alpha to an ESA with an apparent lower cost resulted in a worsening of the anemia of the patients after the conversion. Instead of leading to savings, the conversion actually increased expenditures.

[Reduced nitric oxide bioavailability in chronic renal failure: a new factor of progression?].

Abstract: Nitric oxide (NO) is a gaseous free radical and an important molecular mediator of many physiologic processes in virtually every organ. NO is produced from L-arginine by nitric oxide synthase (NOS). This enzyme is expressed as 3 isoforms, all of which have been isolated from the kidney: endothelial NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS). At present it is very difficult to measure authentic nitric oxide in vivo; a way to circumvent the difficulties is to study the effects of NOS stimulation and subsequent nitric oxide release directly by measurement of the resulting changes in vascular tone. In the kidney and vasculature, NO plays fundamental roles in the control of systemic and intrarenal hemodynamics, the tubuloglomerular feedback response, pressure natriuresis, release of sympathetic neurotransmitters and renin, and tubular solute and water transport. Chronic renal failure (CRF) is a state of NO deficiency secondary to decreased NO production and/or increased bioinactivation of NO by reactive oxygen species. The purpose of this review is to examine the functions of NO in the kidney, and to discuss the effects of NO deficiency in the progression of chronic kidney disease.

[Vascular access in the elderly: AVF vs CVC. A comment].

Abstract: The aging population starting hemodialysis treatment raises the question as to which is the best vascular access in an older patient with multiple complications. The center effect is an important element in the choice of a vascular access, as shown by the DOPPS data and by a recent audit held in Lombardy. However, other data show an increase in the use of permanent CVCs in the last years and other factors must be taken into account in this clinical choice. Also the timing of proposing a vascular access to a patient has changed over the years (see K-DOQI 2006 vs 2000). Most of the literature agrees on the strategy of a global clinical evaluation of the patient to decide when to place a vascular access and which type of access to use. Native and prosthetic fistulas are considered superior to CVCs although the latter have certain advantages in selected patients, such as those with severe cardiac problems. The nephrologist has a major role in vascular access management as part of a team made up also by a vascular surgeon and an interventional radiologist. Only in a center where both native and prosthetic fistulas can be constructed and permanent CVCs be placed can a nephrologist choose the most appropriate vascular access for individual patients after evaluation not only of their renal function but their cardiovascular risk as well.

Stem cells and repair of kidney damage

Abstract: In the adult kidney, different populations of progenitor cells (or stem cells) have been identified. These cells may represent a remnant of embryonic stem cells in the adult tissue, or populations of bone-marrow-derived stem cells homed within the kidney and modified by the local microenvironment. This modification may be the expression of a partial commitment or of different degrees of maturation. Resident stem cells may account for the growth of the organ during development, for the physiological cell turnover, and for the repair of kidney damage. In addition, stem cells derived from the bone marrow and migrated through the circulation to the site of the damage may contribute to tissue repair. Preliminary studies suggest that this regenerative potential of stem cells could be exploited for therapeutic purposes by administration of ex vivo expanded stem cell populations or by development of strategies aimed to expand and differentiate local stem cells.

The role of endothelial progenitor cells in renal disease

Abstract: Recent evidence suggests that injury to the renal vasculature may play an important role in the pathogenesis of both chronic and acute ischemic kidney injury. Early alterations in peritubular capillary blood flow during reperfusion have been documented and associated with loss of normal endothelial cell function. In addition, ischemia induces alterations in endothelial cells that may promote inflammation and procoagulant activity, thus contributing to vascular congestion. Reduction of the microvasculature density increases hypoxia-mediated fibrosis and alters proper hemodynamics, which may lead to hypertension. This may play a critical role in the progression of chronic kidney disease following initial recovery from ischemia/reperfusion-induced acute kidney injury. The turnover and replacement of endothelial cells is therefore an important mechanism in the maintenance of vascular integrity also in the kidney. It is becoming clear that impaired vascular repair mechanisms as a result of a reduced number and/or impaired function of endothelial progenitor cells may contribute to renal disease. Moreover, investigators have begun to identify potential mechanisms responsible for the loss of function of endothelial progenitors in renal disease. In allografts, persistent injury results in excessive turnover of graft vascular endothelial cells. Moreover, chronic damage elicits a response that is associated with the recruitment of both leukocytes and endothelial progenitors, facilitating an overlapping process of inflammation and angiogenesis. In conclusion, angiogenesis and endothelial cell turnover play a pivotal role in renal disease and allograft rejection. Manipulation of these processes might have important implications for the development of novel therapeutic strategies in the near future.

Fractures and chronic renal insufficiency

Abstract: Chronic renal insufficiency (CRI) causes important modifications in the metabolism of phosphorus and calcium, to which frequently resulting in serious disorders of the skeleton, including demineralization, reduction of the bone resistance and a higher risk of fractures. Renal osteodystrophy is the term used to describe these disorders; they are generally heterogeneous and are classified according to the state of bone turnover into secondary hyperparathyroidism, adynamic bone, and osteomalacia. The incidence of hip fractures in the patients with CRI is higher than in the general population. Hip fractures are an important cause of morbidity and mortality. The evaluation of the fracture risk in the patients with different degrees of CRI is problematic, in particular because of the difficulty in identifying fractures, especially vertebral ones. The instrumental index that best expresses the fracture risk in the general population is bone mineral density (BMD); however, the relationship between low BMD and CRI is disputed. Bone disorders in patients with CRI have in fact a multifactorial pathogenesis and low BMD is not the only risk factor for fractures. Besides densitometric evaluation, also that vertebral morphometric evaluation would be desirable in patients with CRI. The fracture risk increases progressively with the severity of chronic renal disease and it is especially high in patients with renal insufficiency in more advanced-stages CRI (creatinine clearance<15-20 mL/min). However, not only in patients with severe CRI undergoing dialysis, but also in those with milder renal disease is the risk of bone fractures high.

[Early detection of chronic kidney disease: epidemiological data on renal dysfunction].

Abstract: Estimated glomerular filtration rate (eGFR) and urinary albumin (U-Alb) have been suggested as indicators for the early identification of persons with kidney dysfunction. The Gubbio Study collected data on serum creatinine, UAlb, other laboratory indices, blood pressure, and medical history in a population sample of 4574 adults (2083 men and 2491 women, age range 18- 95 years). The study included analyses on six disorders which are commonly associated with kidney disease (hypertension, cardiovascular disease, anemia, high serum uric acid, high serum phosphorus/low serum calcium, and high serum potassium). Low eGFR ( 30% at > or =75 years in both sexes, p or =20 microg/min) in the presence of non-low eGFR. Low eGFR was associated with at least two disorders potentially due to kidney disease in the majority of persons but was rarely associated with a previous diagnosis of kidney disease (<5% of cases). These data support the use of eGFR for the screening of people with or at risk of developing kidney disease. Awareness of kidney disease is very low in the Italian population.

The sympathetic system and neuroendocrine hypertension

Abstract: Sporadic pheochromocytoma is a rare tumor that should be taken into account in patients with hypertensive crisis, arrhythmias, and panic disorder. Familial pheochromocytoma is frequently found in subjects with von Hippel-Lindau disease, multiple endocrine neoplasia type II, neurofibromatosis, and SDHD gene mutations. The prevalence of sporadic pheochromocytoma is very low, approximately 0.05% among subjects with essential hypertension and even less in the general population. However, aggressive diagnostic intervention is recommended whenever a pheochromocytoma is suspected because the uncontrolled catecholamine release from the tumor can lead to serious and potentially lethal complications. Plasma free metanephrines have been shown to have high sensitivity and specificity in the biochemical diagnosis of sporadic and familial pheochromocytoma. Measurement of 24-hour urinary fractionated metanephrines may be an acceptable alternative in many patients. The current approach to the diagnostic localization of pheochromocytoma relies on computed tomography (CT), magnetic resonance imaging (MRI) and [123-I] and [131-I] MIBG scintigraphy. CT and MRI have very high sensitivity but low specificity, whereas MIBG scintigraphy has good specificity but its sensitivity is less than optimal, especially for the detection of metastases. In difficult cases, PET imaging appears to be promising.

[Long-term management of renal transplant recipients].

Abstract: Transplantation has been demonstrated to improve the quality of life and long-term survival of patients with end-stage renal disease (ESRD) when compared with dialysis. This has resulted in a progressive increase in patients living with a functioning kidney graft as a percentage of the total ESRD population. Renal transplant recipients require complex long-term medical care, which is straining the limited resources of transplant centers. Moreover, due to considerations of geography or individual preference, a large number of patients, once their condition has stabilized, move away from the transplant center to the local nephrology unit. To facilitate and enhance the specialized care of these patients, it is crucial that nephrology units understand and manage the medical problems affecting long-term transplant recipients (e.g., chronic graft dysfunction, toxicity of immunosuppressive therapy, cardiovascular, infectious and neoplastic complications, hematological issues, bone disease, pregnancy and nonadherence to prescriptions). Regular interactive communication between the nephrology unit and the transplant center optimizes the continuity of care. Practice guidelines and the available literature on the subject are revised and critically analyzed in this paper.

The role of angiogenesis in renal carcinoma

Abstract: Renal cell carcinoma is characterized by intense angiogenesis associated with the inactivation of the von Hippel-Lindau oncosuppressor gene with consequent hyperexpression of proangiogenic factors. Functional and molecular characterization of renal tumor endothelial cells has demonstrated an increase in angiogenesis and cell survival. The proangiogenic phenotype was due to hyperactivation of the PI3K/Akt/mTor pathway, which downregulates the synthesis of the antiangiogenic factor thrombospondin-1. Moreover, renal tumor endothelial cells presented an immature and embryonic phenotype with expression of the embryonic kidney-specific gene PAX-2. It is conceivable that the endothelium present in renal carcinoma is heterogeneous, with a possible origin from adjacent vessels, resident or circulating stem cells, or from the tumor cells themselves. The relevance of the angiogenic process in renal carcinoma is underlined by the therapeutic effect of antiangiogenic drugs. Different drugs against VEGF, such as the anti-VEGF monoclonal antibody bevacizumab, and small molecule tyrosine-kinase inhibitors, such as sunitinib and sorafenib, showed a clinical effect in patients with metastatic carcinoma. However, antiangiogenic therapy, although beneficial, is not sufficient per se. These studies suggest a role for the angiogenic program in the growth and dissemination of renal carcinoma and indicate the need for new therapeutic strategies.

[Low-protein diet and proteinuria].

Abstract: Proteinuria has a direct toxic effect on the kidney and is a predictor of renal disease progression and outcome also in nondiabetic patients. Controlling proteinuria by reducing the dietary protein intake slows the progression of renal damage, as has been demonstrated in many experimental and clinical studies with low-protein diets (LPD). Serum albumin increases in LPD-treated kidney patients due to reduced urinary excretion. Moreover, it has been observed that LPD-treated kidney patients can keep an adequate nitrogen balance. Association of LPD with ACE inhibitors or sartans has an antiproteinuric effect stronger than that of LPD or antihypertensives alone, which is due to their different hemodynamic actions in the kidney. ACE inhibitors and sartans can be contraindicated in patients with stage 5 chronic kidney disease, where LPD is the only option for proteinuria control. Conflicting results with soy protein-based diets advise against the use of such diets in patients with nephrotic syndrome.