Medication is an additional source of phosphate intake in chronic kidney disease patients.

BACKGROUND AND AIMS: Hyperphosphatemia increases the risk of cardiovascular morbidity but the use of medicines as a source of phosphate has not been investigated yet. This study aims to explore the use of absorbable phosphate-containing drugs in CKD patients. METHODS AND RESULTS: Incident CKD patients were identified within the Arianna database (containing data from 158,510 persons in Caserta (Southern Italy) registered with 123 general practitioners) from 2005 to 2011. Drugs prescribed to these patients were classified as phosphate-containing based on the summary of product characteristics (SPC), PubChem and Micromedex. The number and duration of prescriptions for these drugs as well as the overall intake of phosphate were estimated. Out of 1989 CKD patients, 1381 (70%) were prescribed 266 medicinal products containing absorbable phosphate over a median follow-up of 6 years (interquartile range (IQR) = 5.2-6.0). Most patients were prescribed ATC A (650; 47.1%) and C (660; 47.8%) phosphate-containing drug products targeting the gastrointestinal and cardiovascular system for a median of 232 (IQR: 56-656) and 224 (IQR: 56-784) days respectively. CONCLUSIONS: Several medications, especially chronically prescribed ones, contain absorbable phosphate. This study's findings confirm the relevance of medicines as a phosphate source for the first time.

HLA haplotype in a patient with systemic lupus erythematosus triggered by hepatitis B vaccine.

AIM: Find an association between hepatitis B vaccine-related systemic lupus erythematosus and HLA. MATERIAL: A 27-year-old woman who developed a lupus nephritis after the administration of hepatitis B vaccine. METHODS: We studied HLA antigen expression on lymphocytes and genomic haplotype. Class I-II HLA antigen typing was performed by the microlymphocytotoxicity test with the standard NIH method, and Class I-II HLA allele typing by polymerase chain reaction, using single-strand oligonucleotide dot-blot kits. RESULTS: The serological haplotype was HLA A24/25, B18 (Bw6)/-, C-/-, DQ7/-, DR11(5)/52. The genomic haplotype was A*2403/2504, B*1825/1825, C*1207/ 1207, DRB1*1102/1132, DRB3*0202/0202, DQA1*0505/0505, DQB1*0301/0301. Then we sought for analogies with haplotypes known to be related to other systemic AID. Since we have found HLA alleles typical both of systemic lupus erythematosus and Sjogren's syndrome, the persistence of ENA-SSA positivity was highly suspicious for a possible overlap syndrome. CONCLUSIONS: Hepatitis B vaccine can potentially trigger both the onset or the exacerbations of several autoimmune disorders, including systemic lupus erythematosus, by reduced immune complex clearance or molecular mimicry. This study represents the first report on the association between hepatitis B vaccine related systemic lupus erythematosus and HLA. Probably autoimmune reactions triggered by vaccines occur only in predisposed subjects, in which antigen presentation influenced by HLA haplotypes leads to the autoimmune cascade. More studies are needed to corroborate our hypothesis. They could disclose new pathways in the field of prevention.

Vascular access for hemodialysis and cardiovascular complications.

Native arterio-venous fistula (AVF), is the first choice of the vascular access for hemodialysis treatment. In comparison with other vascular accesses such as prosthetic arterio-venous graft or permanent central venous catheter, AVF has shown a significant reduction in cardiovascular mortality. It needs, of course, an appropriate blood flow that provides a flow of 400-800 mL/min in the distal seat and a flow of 800-1500 ml/min in the proximal seat. As a consequence, the creation of AVF may be associated with changes in blood flow, pulmonary pressure and cardiac output. All these haemodynamic changes may not have any cardiac consequences, or they could lead to congestive heart disease particularly when the blood flow of AVF is greater than 2000 ml/min. For this reason, the patient's cardiac status should determine the choice of dialysis and the type of vascular access. Cardiac function monitoring is essential, particularly when dealing with patients at high risk for congestive heart disease and AVF in the proximal seat. Vascular access reduction surgery may be effective in some cases, otherwise a suitable alternative could be that of closing AVF. However, the likely side effects that can be generated by closing arterio-venous AVF such as a sudden increase of venous peripheral systemic should be taken into account.

[Management of hyperphosphatemia in patients with chronic kidney disease]. / Il controllo della fosforemia nell'insufficienza renale cronica.

Hyperphosphatemia is a common finding in patients with chronic kidney disease (CKD) undergoing hemodialysis or receiving conservative treatment. Recent papers have reported a link between hyperphosphatemia, soft tissue calcifications, and cardiovascular events responsible for high morbidity and mortality in these patients. Our group identified in salivary phosphate secretion a method to study the phosphate balance in CKD. Moreover, we found that CKD patients on hemodialysis usually drink beverages with a high phosphate content that may increase their serum phosphorus levels. Hyperphosphatemia is currently treated with diet, phosphate-binding drugs, and drugs acting on bone metabolism. Despite such treatment, only half of the patients with end-stage renal disease fall within the K/DOQI guidelines range for serum phosphorus levels. This paper reports positive results obtained with the use of the polymer chitosan as a phosphatebinding chewing gum in CKD patients undergoing periodic hemodialysis.

[Health care based on patients' needs]. / Costruire una Sanita' che parta dalle esigenze dei malati.

Survival is not enough. We need to build a health system starting from patients' needs without wasting the resources of our grandchildren and great-grandchildren. We have to switch from curative to preventive medicine by firing managers who think they can resolve all problems by cutting expenditures. We need to educate a new cadre of managers able to govern by centering the system on the patients. Managers should consider health care as an asset and should reinforce clinical research. Such a program has been recently adopted in France.

[Nursing and quality of life in CKD]. / L'infermiere e la qualita' della vita nella CKD.

Quality of life is one of the main targets of modern medicine. This applies specifically to people suffering from chronic diseases, who are frequently hospitalized and receive continuing care for their irreversible condition. Among chronic diseases, end-stage renal disease is extremely interesting because it can be assessed transversely in different settings but also longitudinally over time, thus allowing adequate evaluation of quality of life.

[Erectile dysfunction and quality of life in patients with chronic renal failure]. / Disfunzione sessuale e qualità di vita nel paziente con insufficienza renale cronica.

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.

Seminal vesicle cysts with unilateral renal agenesis and contralateral ureteral stenosis in a beta-thalassemic patient: an unknown association by incomplete development of the mesonephric duct.

We report the case of a 13-year-old male patient with beta-thalassemic trait who presented for a colic pain. An ultrasound of the abdomen revealed absence of the right kidney with a complex hypoechogenic pelvic mass causing mild pressure on the posterior bladder wall. Urography showed hypertrophy of the left kidney with moderate ureteral enlargement of the distal third due to an insertion defect in the bladder suggestive of a primary segmental nonobstructing megaureter. MR studies showed right multilocular seminal vesicle cysts. One year later an MR examination of the pelvis showed an increase in size of seminal vesicle cysts and open surgery was performed to remove the cystic retrovesical mass. Our case represents a very rare association of seminal vesicle cysts, unilateral renal agenesis and alteration in contralateral ureteral insertion in a patient with beta-thalassemic trait.

A new approach to the evaluation of hyperphosphatemia in chronic kidney disease.

AIMS: Hyperphosphoremia, main contributor to cardiovascular calcifications, has a major impact on the morbidity and mortality of chronic renal failure (CRF) patients. Phosphate binders and dietary phosphate limitation are not effective enough to abolish hyperphosphoremia-induced cardiovascular abnormalities, therefore, the identification of other and more timely approaches for serum phosphorous reduction is necessary. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000 - 1,800 ml), deserves attention as a marker for an earlier start of pharmacologic treatment for phosphorous removal. In ESRD patients under dialysis we have shown increased salivary phosphate closely to be related with serum phosphorous and interpreted as compensatory. This study evaluates salivary phosphate secretion in 77 nondialyzed CRF compared with healthy subjects and its relationship with renal function. METHODS: Saxon's test confirmed normal salivary function in patients and controls. Serum phosphorous, creatinine and GFR were also measured. RESULTS: Salivary phosphorous was significantly higher in CRF patients compared with controls: 38.60 mg/dl (range 12.20 - 95.60) vs 16.30 (10.30 - 27.10), p < 0.0001; serum phosphate was also significantly higher: 3.70 (2.10 - 6.80) vs 3.50 (2.3 4.6), p = 0.013. In CRF patients, salivary phosphorous positively correlated with serum phosphorous (r - 0.45, p < 0.0001) and with serum creatinine (r = 0.72, p < 0.0001), while negatively correlated with GFR (r = -0.72, p < 0.0001). CONCLUSIONS: The results of our study show also in CRF patients increased salivary phosphate secretion, which is related with renal function. On this basis the use of salivary phosphate secretion as a marker for an earlier start of the abnormal phosphate, metabolism pharmacologic treatment could be proposed.

Sevelamer worsens metabolic acidosis in hemodialysis patients.

BACKGROUND: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate. METHODS: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated. RESULTS: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1 mEq/L, whereas it averaged 21.1 +/- 0.7 mEq/L in patients on calcium carbonate (p<0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p<0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.

Global approach to cardiovascular risk in chronic kidney disease: reality and opportunities for intervention.

The current implementation into nephrology clinical practice of guidelines on treatment of cardiovascular (CV) risk factors in chronic kidney disease (CKD) is unknown. We designed a cross-sectional analysis to evaluate the prevalence and treatment of eight modifiable CV risk factors in 1058 predialysis CKD patients (stage 3: n=486; stage 4: n=430, stage 5: n=142) followed for at least 1 year in 26 Italian renal clinics. The median nephrology follow-up was 37 months (range: 12-391 months). From stages 3 to 5, hypertension was the main complication (89, 87, and 87%), whereas smoking, high calcium-phosphate product and malnutrition were uncommon. The prevalence of proteinuria (25, 38, and 58%), anemia (16, 32, and 51%) and left ventricular hypertrophy (51, 55, and 64%) significantly increased, while hypercholesterolemia was less frequent in stage 5 (49%) than in stages 4 and 3 (59%). The vast majority of patients received multidrug antihypertensive therapy including inhibitors of renin-angiotensin system; conversely, diuretic treatment was consistently inadequate for both frequency and dose despite scarce implementation of low salt diet (19%). Statins were not prescribed in most hypercholesterolemics (78%), and epoietin treatment was largely overlooked in anemics (78%). The adjusted risk for having a higher number of uncontrolled risk factors rose in the presence of diabetes (odds ratio 1.29, 95% confidence interval 1.00-1.66), history of CV disease (odds ratio 1.48, 95% confidence interval 1.15-1.90) and CKD stages 4 and 5 (odds ratio 1.75, 95% confidence interval 1.37-2.22 and odds ratio 2.85, 95% confidence interval 2.01-4.04, respectively). In the tertiary care of CKD, treatment of hypertension is largely inadequate, whereas therapy of anemia and dyslipidemia is frequently omitted. The risk of not achieving therapeutic targets is higher in patients with diabetes, CV disease and more advanced CKD.

[Evolution of the classification of acute and chronic transplant rejection]. / Evoluzione della classificazione del rigetto acuto e cronico del trapianto.

In the last twenty years, several systems have been proposed to codify renal allograft rejection. The Banff classification for kidney allograft pathology, introduced in 1993, started a new era in the standardization of criteria for rejection and for allowing uniform reporting. This consensus on allograft grading proposed a scheme to guide therapy in transplant patients and to help establish an objective rejection end point in clinical trials. This scheme, modified during 1993-1997 to address many of the criticisms, was substantially improved. Another important system of classification of allograft renal biopsies was the Cooperative Clinical Trials in Transplantation (CCTT) classification which was published in 1997. The aim of this system was to develop a schema that would be practical to implement, easy to describe to unfamiliar personnel, reproducible, with high rates of sensitivity and specificity and clinically informative (predictive of course and/or response to therapy). In March 1997, a fundamental revision of the Banff classification for acute rejection was achieved by a consensus conference for incorporating many of the strengths of the CCTT system. Some of these were the importance of vascular damage (endoarteritis, endothelial activation, fibrinoid necrosis) and interstitial hemorrhage, but not the interstitial infiltrate or tubulitis, which correlated with response to anti-rejection therapy and/or 1 year clinical outcome. The most recent modification concerns the addition of C4d-positive acute humoral rejection and the emphasis on differences between cell-mediated and antibody-mediated rejections. Future refinements of these classifications and findings of new molecular markers of allograft rejection, such as fas-ligand or granzyme-B, will help to improve diagnosis and therapy in renal transplant patients.

Therapy of kidney diseases in poor people in France during the 18th century.

The idea of using simple and easily available remedies to treat different diseases is typical of ancient medicine and one of the first examples can be found in Galen's works. This type of Medicine was called ""Medicine for the poor"" in the 18th century. This expression refers to the use of simple substances, available in nature, like plants, herbs, flowers, fruit, minerals etc, to treat some of the more common diseases. Evidence of this tendency in the early 18th century is a textbook of Medicine written in France by Dubé in 1669. This work has been reprinted several times, and translated from French into English in 1704 and into Italian in 1715 by Sebastiano Castellini. In his work Dubè describes the therapeutic remedies made with natural substances. Some of these substances were used to treat renal diseases, in particular nephrolithiasis, kidney and bladder inflammatory disease, renal ulcer, dysuria and incontinence.

Involvement of interleukin-18 in patients on maintenance haemodialysis.

Maintenance dialysis induces a clinical state of immunodeficiency. The pathway of circulating T cells from haemodialyzed patients is changed and characterized by an increase of Th1 cells. The unbalanced T helper differentiation derives from an altered regulation of interleukin-12 (IL-12), which represents an important inducer of Th1. IL-18 is a pro-inflammatory cytokine expressed by a variety of cell types that is structurally related to the Th1 family and shares biological properties with IL-12 as the promotion of Th1 responses. To explain the involvement of IL-18 in the typical disorders of dialysis, we analyzed IL-18 serum levels in a group of haemodialyzed patients. We enrolled 16 patients on chronic haemodialysis (HD) treatment for end-stage renal failure and 16 healthy volunteers as the control group. IL-18 levels were assessed by immunoenzymatic methods (detection limit was <12.5 pg/ml). HD patients strongly showed higher IL-18 serum levels compared to healthy donors (508.47 +/- 314.39 vs. 193.44 +/- 56.33 pg/ml, p < 0.005). Moreover, IL-18 levels in HD directly correlated to dialytic age (Rho = 0.544, p = 0.0419) and indirectly to Kt/V (Rho = 0.703, p = 0.0086). Our data represent the first evidence of the relation between IL-18 serum levels and HD. In the light of our results, we think that the unbalanced T helper differentiation may depend, at least in part, on an abnormality in the IL-18 production.