Incidence of primary and second cancers in renal transplant recipients: a multicenter cohort study.

Limited data exist about cancer prognosis and the development of second cancers in renal transplant recipients. In a retrospective cohort study on 3537 patients incidence rates of the first and, if any, of a second cancer, and standardized incidence ratios [SIR (95% CI)] were computed. Two hundred and sixty-three (7.5%) patients developed a NMSC, and 253 (7.2%) another type of cancer after a median follow-up of 6.5 and 9.0 years, respectively. A statistically significant excess risk, if compared to an age- and sex-matched reference general population, was observed for Kaposi sarcoma and NMSC, followed by non-Hodgkin lymphoma and carcinoma of cervix uteri; a small number of unusual cancers such as tumors of the salivary glands, small intestine and thyroid also were detected at a level worthy of additional scrutiny. Ten-year survival rate of all noncutaneous cancers was 71.3%, with lower rates for lung carcinoma and non-Hodgkin lymphoma (0% and 41.7%, respectively). Patients with NMSC had an increased risk of developing a second NMSC [SIR 8.3 (7.0-10.0)], and patients with a primary noncutaneous cancer had increased risk of developing a second noncutaneous cancer [SIR 1.8 (1.2-2.8)], if compared to the whole cohort. Our study underscore that the high risk of primary and second cancer in renal transplant recipients, including unusual cancers.

PTCH1 gene haplotype association with basal cell carcinoma after transplantation.

BACKGROUND: Basal cell carcinoma (BCC) is 10 times more frequent in organ transplant recipients (OTRs) than in the general population. Factors in OTRs conferring increased susceptibility to BCC include ultraviolet radiation exposure, immunosuppression, viral infections such as human papillomavirus, phototype and genetic predisposition. The PTCH1 gene is a negative regulator of the hedgehog pathway, that provides mitogenic signals to basal cells in skin. PTCH1 gene mutations cause naevoid BCC syndrome, and contribute to the development of sporadic BCC and other types of cancers. Associations have been reported between PTCH1 polymorphisms and BCC susceptibility in nontransplanted individuals. OBJECTIVES: To search for novel common polymorphisms in the proximal 5' regulatory region upstream of PTCH1 gene exon 1B, and to investigate the possible association of PTCH1 polymorphisms and haplotypes with BCC risk after organ transplantation. METHODS: Three PTCH1 single nucleotide polymorphisms (rs2297086, rs2066836 and rs357564) were analysed by restriction fragment length polymorphism analysis in 161 northern Italian OTRs (56 BCC cases and 105 controls). Two regions of the PTCH1 gene promoter were screened by heteroduplex analysis in 30 cases and 30 controls. RESULTS: Single locus analysis showed no significant association. Haplotype T(1686)-T(3944) appeared to confer a significantly higher risk for BCC development (odds ratio 2.98, 95% confidence interval 2.55-3.48; P = 0.001). Two novel rare polymorphisms were identified at positions 176 and 179 of the 5'UTR. Two novel alleles of the -4 (CGG)(n) microsatellite were identified. No association of this microsatellite with BCC was observed. CONCLUSIONS: Haplotypes containing T(1686)-T(3944) alleles were shown to be associated with an increased BCC risk in our study population. These data appear to be of great interest for further investigations in a larger group of transplant individuals. Our results do not support the hypothesis that common polymorphisms in the proximal 5' regulatory region of the PTCH1 gene could represent an important risk factor for BCC after organ transplantation.

[Quality of life of the elderly patient on dialysis]. / La qualita' della vita nell'anziano in dialisi.

When elderly patients with end-stage renal disease start dialysis their quality of life, and particularly the emotional aspects of it, are very similar to those of age-matched controls. However, as the treatment becomes chronic the quality of life will decline not only with regard to the physical aspects (due to comorbidities) but also the emotional aspects. Dialysis-related stress episodes and the peculiar interrelationships in the dialysis facility setting may cause psychological discomfort which on the one hand reduces the patient's quality of life and on the other may unfavorably impact on the family and the health-care personnel. An integrated psychological approach involving the patient from the beginning of dialysis throughout the treatment process as well as the healthcare personnel and the family can reduce the patient's psychological discomfort, thereby improving quality of life.

[Dialysis, adaptation, quality of life, and family support]. / Rapporti tra adattamento, qualità di vita e supporto familiare, sociale nel paziente in trattamento dialitico.

Chronic dialysis treatment is characterized by a series of complex interdependent objective problems, such as the dialysis experience, the individual way to assess it, and some "protective" factors such as social and family support. Progresses in dialysis research show that dialysis patients have important alternatives to passively accept their condition: thanks to adequate psychological and relational aid, they can reach rather advanced adaptation levels, which allow them to modify both their behaviour and way of life, to keep a satisfactory compliance, and to improve their quality of life (QoL). In this adaptation process, both family and social support play an important role, although controversy still exists on it. The results of our study confirm the complexity of this role and show that either haemodialysis or peritoneal dialysis patients' adaptation process and QoL may be directly related to the extent of family member's ("caregiver") support. It is of particular interest the fact that patients, especially those undergoing haemodialysis, provided with a caregiver's assistance but who choose to "act by themselves", do have better adaptation levels and QoL than those who rely only on their caregiver. This fact reassesses the widely accepted point of view that continuous caregiver's support is always a positive and necessary factor in order to improve both the adaptation and the QoL of dialysis patients.

Evaluation of glyoxal and methylglyoxal levels in uremic patients under peritoneal dialysis.

Advanced glycation end products (AGEs) accumulate in serum and tissues of patients with chronic renal failure, even in the absence of diabetes, and a different clearance of these species has been observed by hemodialysis and peritoneal dialysis (CAPD). Furthermore, it has been shown that not only AGE but also 1,2-dicarbonyl compounds are formed during heat sterilization of glucose-based peritoneal dialysis fluids. Therefore, we investigated the level of some AGEs (pentosidine and free pentosidine) and dicarbonyl compounds (glyoxal and methylglyoxal) in end-stage renal disease patients subjected to peritoneal dialysis. Samples (20 from healthy subjects, 16 from uremic patients before and after 12 h of peritoneal dialysis) were analyzed, and the plasma and dialysate levels of glyoxal, methylglyoxal, pentosidine, and free pentosidine were determined. In plasma of uremic patients, mean values of pentosidine showed a small decrease after dialysis and were always higher than those of healthy control subjects. An analogous trend was observed for free pentosidine. In the case of peritoneal dialysate, no pentosidine and free pentosidine were found at time zero, whereas both compounds were detected after 12 h of dialysis. Glyoxal and methylglyoxal mean levels showed a decrease in plasma after dialysis even if their values were always higher than those of healthy control subjects. Surprisingly, an analogous trend was observed also in dialysate. These results might indicate that glyoxal and methylglyoxal already present in the dialysis fluid react with the peritoneal matrix proteins, accounting for the gradual loss of peritoneal membrane function that is often observed in patients subjected to CAPD for a long time.

Serum lipids in patients with chronic renal failure on long-term, protein-restricted diets.

Disordered lipid metabolism is believed to play an important role in accelerating the progression of chronic renal disease toward uremia. We examine this hypothetic role of lipids in a large population of patients on long-term dietary protein restriction. In our experience, there is no conclusive evidence that lipids may accelerate the progression of functional deterioration in patients with reduced renal function. Hyperlipidemia seems to be only one among the many factors affecting the prognosis of primary renal disease. Dietary protein restriction is effective in maintaining normal or only slightly elevated serum lipid levels in patients with early renal failure. Moreover, patients with renal failure maintained on this diet, which provides an elevated ratio of polyunsaturated to saturated fatty acids, have a more favorable lipid composition of erythrocyte membrane (low percentage of saturated fatty acids and high percentage of polyunsaturated fatty acids) when compared with patients on an unrestricted diet.

Captopril in patients with type II diabetes and renal insufficiency: systemic and renal hemodynamic alterations.

PURPOSE: To our knowledge, clinical studies on the long-term use of angiotensin converting enzyme inhibitors in patients with type II diabetes mellitus and nephropathy with incipient renal failure are nonexistent. We therefore assessed the effects of long-term treatment with captopril on systemic and renal hemodynamics and urinary protein excretion in patients with type II diabetes mellitus and the clinical syndrome of diabetic nephropathy. PATIENTS AND METHODS: Twelve patients, 10 men and two women, with an average age of 52 years (range, 40 to 66), participated in the study. After the basal hemodynamic evaluation, the patients received captopril in two daily doses. The dosage was adjusted at weekly intervals in order to obtain normalization of blood pressure without exceeding the maximum allowable dosage. Four patients also received furosemide (20 to 40 mg/day). RESULTS: After six months of treatment, the intra-arterial blood pressure fell (from 162 +/- 17/103 +/- 5 to 139 +/- 26/89 +/- 10 mm Hg) due to the reduction in total peripheral vascular resistance index (from 3,720 +/- 658 to 3,190 +/- 762 dynes/second/cm-5/m2), with no change in cardiac index (2.78 +/- 0.36 to 2.79 +/- 0.47 liters/minute/m2). No significant change was seen in renal vascular resistance (from 30,175 +/- 5,371 to 30,173 +/- 5,372 dynes/second/cm-5/1.73 m2) and in filtration fraction (from 26 +/- 8 to 27 +/- 10 percent). A slight, not significant, decrease in renal plasma flow (from 243 +/- 97 to 217 +/- 108 ml/minute/1.73 m2), in glomerular filtration rate (from 57 +/- 17 to 51 +/- 19 ml/minute/1.73 m2), and in proteinuria (from 4.50 +/- 3.10 to 3.40 +/- 2.31 g/day) was also observed. CONCLUSION: Our findings suggest that captopril is an effective antihypertensive agent in patients with diabetic nephropathy, but the renal beneficial effects seem to be limited when this syndrome is complicated by renal insufficiency.

Renal reserve in patients with solitary kidneys.

The first part of this article focuses on the risk of functional deterioration in subjects with solitary kidneys; the long-term clinical outcome of various subgroups of patients is reviewed. Thereafter, the pathophysiology of the renal functional reserve in subjects with a 50% reduction in renal parenchyma and the results coming from studies eliciting the renal reserve in these subjects are summarized. Finally, the clinical significance of the renal functional reserve and its usefulness in clinical practice are critically discussed.

Effect of dietary manipulation on the lipid abnormalities in patients with chronic renal failure.

Disorders of lipid metabolism could play an important role in mediating the progression of chronic renal disease toward uremia. The hypothesis of the nephrotoxicity of lipids has been considered in a large population of patients on long-term dietary protein restriction. In our experience, there is no evidence that lipid disorders may accelerate the progression of renal disease. Hypercholesterolemia and/or hypertriglyceridemia are probably only some of the many factors affecting the prognosis of renal disease. Dietary protein restriction seems to be effective in maintaining normal or only slightly elevated serum lipids in patients with early renal failure, even after years of dietary treatment, despite the natural progression of renal functional deterioration. Moreover, this dietary regimen has a favorable effect on lipid composition of erythrocyte membrane when compared with those of patients on a free diet.

Early dietary protein and phosphorus restriction is effective in delaying progression of chronic renal failure.

A diet containing about 40 kcal/kg, 0.6 g/kg of protein, 700 mg of phosphorus, and 1,000 to 1,500 mg of calcium (orally supplemented) was prescribed to three groups of patients with chronic renal failure for 6 to 76 months. The mean serum creatinine values were 2.18 mg/dl in group 1 (25 patients), 4.24 mg/dl in group 2 (20 patients), and 6.10 mg/dl in group 3 (8 patients). An additional group of 30 patients (group 4) who had followed no specific dietary treatment for 3 to 72 months was taken as control. The plots of reciprocal serum creatinine against time gave slopes of -0.0008, -0.0010, and -0.0041 in the three groups of patients on the protein-restricted diet, and a slope of -0.020 in the patients on the free diet. The differences between the slopes in patients in groups 1, 2, and 3 versus that in patients in group 4 are statistically significant (analysis of variance and F ratio: P less than 0.01). During the follow-up period a decline in reciprocal serum creatinine greater than the mean values in the whole group was observed in 37.5% of patients in group 3, in 20% of those in group 2, and in only 12% of those in group 1. Thus, the degree of functional renal deterioration is critical in modulating the effects of dietary protein and phosphorus restriction. Several nonimmunologic factors, including hypertension, infection, electrolyte abnormalities, and low-calorie intake, appeared to play an important role in influencing the rate of progression of renal failure in patients on dietary protein restriction.

Hypertension and progression of renal disease.

That systemic hypertension is involved in the progression of human renal disease is mostly suggested by the way anti-hypertensive treatment affects the course of the disease. Clinical evidence has been obtained from observational studies as well as from studies of dietary protein restriction. In addition, several trials have compared the effects of different antihypertensive agents. The angiotensin-converting-enzyme inhibitors have the best renoprotective effect when compared to conventional agents and calcium channel blockers. In most studies, ACE-inhibitors approximately halved the risk of progressive renal functional deterioration in patients with non-diabetic nephropathies; this protection was associated with a significant reduction in systemic blood pressure and proteinuria. Statistical analysis, however, also suggests a direct effect of ACE-inhibitors on the kidney.

Biofiltration in the treatment of patients with acetate dialysis intolerance.

Nine patients with intolerance to acetate hemodialysis were treated with biofiltration. It consisted of a 4 hour acetate hemodialysis during which an additional 2 liters of ultrafiltrate was replaced by a bicarbonate solution (100 mEq/l). Hypotensive episodes disappeared and six out of nine patients were symptomless during the session. Compared to standard hemodialysis, arterial blood bicarbonate and pO2 did not drop during biofiltration. Serum acetate levels, which were abnormally high in patients during standard hemodialysis, were reduced during biofiltration to the levels of a control group of acetate tolerant patients. Our data show that positive clinical results are obtained with biofiltration and suggest that they can be due to a better cellular metabolism of acetate induced by the bicarbonate infusion.

Effect of dietary proteins and lipids in patients with membranous nephropathy and nephrotic syndrome.

Twenty-four patients with idiopathic membranous nephropathy, long-lasting nephrotic syndrome and serum creatinine less than 2 mg/dl ate sequentially, in a randomized cross-over design, a normal protein diet containing 1.1 +/- 0.3 g/kg/day of proteins and a low protein diet containing 0.7 +/- 0.1 g/kg/day of protein, each diet for a period of 3 months. Both diets were low in fat (less than 30% of total calories) and cholesterol (less than 200 mg/day) content and rich in polyunsaturated fatty acids and in linoleic acid (10% of energy). Random assignment to one of the two 3 month diet periods was done after a RUN-IN period of at least one month on the hypolipidic normal protein diet. Glomerular filtration rate (inulin clearance), 24 hour urinary protein loss and serum albumin concentration did not significantly differ at the end of the two diet periods, indicating that long-term restriction of protein intake does not modify GFR or urinary protein loss in nephrotic patients. Serum total and LDL-cholesterol and daily proteinuria were significantly lower at the end of both diet periods than at the beginning and at the end of the RUN-IN period. We suggest that these changes were a consequence of the manipulation of dietary fat intake.

Selenium status and plasma glutathione peroxidase in patients with IgA nephropathy.

The abnormal proliferation of mesangial cells with IgA deposition in the glomeruli characterizes primitive mesangial glomerulonephritis (IgA nephropathy, IgAN); this disease reduces the normal renal parenchyma while renal function becomes progressively impaired. The possible role of selenium has never been considered in evaluating factors involved in the pathogenesis of IgAN. In this work we compared the Se status of 14 IgAN patients (8 with normal renal function, IgAN NRF; 6 with impaired renal function, IgAN IRF) to that of 14 normal individuals (CG NRF) before and after an oral supplementation with selenite (0.13 mol Se/kg b.w./day for 60 days). The following indices of Se status were measured: Se in plasma and urine samples by PIXE; glutathione peroxidase activity in the cytosol of platelets (PLTs-GSH-Px) and of erythrocytes (RBCs-GSH-Px). Both concentrations and activities of plasma glutathione peroxidase (pl-GPx), a selenoenzyme mainly synthesized in and secreted by the kidney, were measured in plasma samples and results compared among groups. IgAN patients showed lower pl-Se and lower activities of selenoenzymes than normal controls before Se supplementation (p < 0.001). These findings suggest that an impaired Se status coexisted with the proliferation of mesangial cells in patients. Selenite induced PLTs-GSH-Px activity in all individuals (p < 0.001), but no variation was observed in RBCs-GSH-Px activity or in the concentration of pl-GPx in the plasma. On the other hand, selenium induced pl-GPx activity in CG NRF (p < 0.001) and in IgAN NRF (p < 0.01), but poorly stimulated pl-GPx activity in IgAN IRF (p = n.s.). However, only 17% and 25% of the pl-GPx activity of normal controls was measured in the plasma of IgAN IRF and IgAN NRF patients, respectively (p < 0.001). In conclusion, selenite only partially restored a normal Se status in patients whose low pl-GPx activity probably reflects an impaired synthesis of this protein as a consequence of reduced normal functioning of the parenchyma in kidneys affected by IgA nephropathy.

Nutrition and the kidney: how to manage patients with renal failure.

Nutrition is believed to play a key role in the management of chronic and acute renal failure. Considerable evidence suggests that unrestricted protein diets accelerate the progression of chronic renal failure. As a result, recommendations have evolved limiting the quantity and quality of nitrogen intake with the goal of slowing the progression to dialysis dependency. Acute renal failure offers different challenges in view of its common association with hypermetabolic states. With respect to nitrogen substrate administration, the use of mixed formulations of essential plus nonessential amino acids seems to be as effective as essential amino acids alone.

Clinical status and acid-base balance during biofiltration in patients with acetate dialysis intolerance.

Nine patients intolerant to acetate hemodialysis were treated with biofiltration. This consisted in a 4-h acetate hemodialysis during which an additional 2 liters of ultrafiltrate were replaced by a bicarbonate solution (100 mEq/l). Hypotensive episodes disappeared and six out of nine patients were symptom-free during the session. Compared to standard hemodialysis, arterial blood bicarbonate and pO2 did not drop during biofiltration. The anion gap did not change during standard hemodialysis, but was significantly reduced during biofiltration (24.5 +/- 2.9 vs 19.9 +/- 1.4 mEq/l). In our conditions clinical results were positive with biofiltration. On the basis of anion gap changes and preliminary results of plasma acetate determinations, it is suggested that a better cellular metabolism of acetate may be induced by bicarbonate infusion.

[Risk factors for the progression of chronic kidney failure]. / I fattori di rischio per la progressione dell'insufficienza renale cronica.

Virtually all renal diseases progress, although at different rates, to end-stage renal failure. The main clinical factors which may explain such relentless progression are reviewed and include: the underlying renal pathology, with the most rapid progression rate observed in glomerular disease and in polycystic kidney disease; systemic hypertension, a significant risk factor for progression in any renal disease; the magnitude and duration of proteinuria with the fastest progression rate found in the nephrotic syndrome; the degree of functional renal deterioration at which so called conservative treatment is prescribed. The proper identification of these risk factors may result in rational dietary and non-dietary intervention with the aim of slowing the progression of chronic renal disease.

[Coronary angiography in uraemic patients awaiting kidney transplantation]. / L'indagine coronarografica negli uremici in lista di attesa per trapianto renale.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in uraemia. Coronary angiography (CA) in patients awaiting kidney transplantation (PAKT) is still a matter of debate. In order to evaluate atherosclerotic coronary damage in PAKT, CAs of 12 PAKT were matched with those of 13 dialysis patients (P) affected by ischaemic heart disease IHD. METHODS: Age sex, length of time on renal replacement therapy, diabetes, smoking and hyperphosphataemia history, clinical diagnosis of IHD, cerebrovascular (CV) and peripheral vascular (PV) disease, mean blood pressure (BP), cholesterol, triglycerides, calcium, phosphate, albumin, haemoglobin, haematocrit and weekly dose of erythropoietin (EPO-dose) were derived from clinical records. RESULTS: PAKT were younger (48 9 vs 63 9 years, p < 0.01) and had higher diastolic BP values (86+/-10 vs 79+/-4 mmHg, p < 0.05) than IHD P. On the contrary all the other parameters investigated were not different in the two groups of P. Prevalence of IHD in PAKT was 16% while frequency of CV and VP disease were not different in the two groups. In 9 of IHD P stenotic lesions >/=75% of normal reference segment were diagnosed in 3 or more vessels whilst in PAKT there were atherosclerotic lesions in right coronary artery, left anterior descending artery and left circumflex artery in 41, 66 and 33% respectively. Narrowing percentage of the coronaries in PAKT and IHD P were: right coronary artery 27+/-42 vs 75+/-35, p < 0.05, left anterior descending artery 29+/-25 vs 86+/-15, p < 0.001, left circumflex artery 11 16 vs 47+/-38, p < 0.05 respectively. CONCLUSIONS: Our study shows that atherosclerotic coronary damage is present in PAKT and, although not hemodynamically significant, it could be an important risk factor for clinical expression of IHD. We conclude that CA should be performed in PAKT especially in those over 45 years.