Conversion from cyclosporine microemulsion to tacrolimus in stable kidney transplant patients with hypercholesterolemia is related to an improvement in cardiovascular risk profile: a prospective study.

The aim of this prospective multicenter study was to evaluate the effect of conversion from cyclosporine (CsA) to tacrolimus (Tac) on cardiovascular risk factors in stable kidney transplant patients with hyperlipidemia. Twenty-six patients were switched from CsA to Tac at 81.7 +/- 44.4 months after transplantation. Tac was started at 0.15 mg/kg/d. Patient outcomes were evaluated up to 6 months after conversion. Significant reductions were seen in systolic blood pressure (143 +/- 13 baseline to 136 +/- 9 mm Hg at 6 months, P = .026) as well as the need for antihypertensive medication, with no changes in diastolic blood pressure. There was a significant reduction in total cholesterol (247 +/- 41 to 221 +/- 35 mg/dL, P = .003), low-density lipoprotein cholesterol (150 +/- 24 to 127 +/- 27 mg/dL, P = .001), total cholesterol/high-density lipoprotein (HDL) cholesterol ratio (4.9 +/- 1.9 to 3.9 +/- 1, P = .02), and triglyceride levels (228 +/- 175 to 148 +/- 71 mg/dL, P = .026). No significant modifications in HDL cholesterol, Apo A1 and Apo-B levels, or in the need for lipid-lowering medication were observed. Glucose levels did not change, but an increase in HbAC1 took place (5.8 +/- 1.1 to 6.2 +/- 1, P = .002). In men Framingham risk score significantly decreased from 11.5 +/- 11.3 to 8.4 +/- 7.2. (P = .0023). In conclusion, elective conversion from CsA to Tac in stable kidney transplant patients with hyperlipidemia was related to an improved blood pressure and lipid profile, both suggesting a decrease in the estimated 10-year coronary heart disease risk in men.

Amino acid losses during hemodialysis with polyacrylonitrile membranes: effect of intradialytic amino acid supplementation on plasma amino acid concentrations and nutritional variables in nondiabetic patients.

BACKGROUND: Malnutrition is highly prevalent in hemodialysis patients. Amino acid (AA) losses during the dialysis procedure may be a contributing factor. OBJECTIVES: The objectives of this study were 1) to prospectively evaluate AA losses and their effect on plasma AA concentrations during dialysis with polyacrylonitrile at baseline and after administration of AAs by intradialysis and 2) to investigate the effects of intradialytic AA supplementation on nutritional status. DESIGN: Seventeen stable patients without diabetes who were receiving hemodialysis were studied. In the first phase, AA losses were evaluated over 2 wk in 10 patients randomly assigned to receive AA supplementation. AA losses were analyzed during the first week without supplementation and during the second week with AA administration. In the second phase, the patients' nutritional status was investigated after 3 mo of AA supplementation and was compared with those in 7 patients not receiving AAs. RESULTS: Mean +/- SD) AA losses during a 4-h dialysis session were 12 +/- 2 g; there was a significant decrease in plasma AA concentrations (386 +/- 298 micromol/L for essential and 902 +/- 735 micromol/L for nonessential AAs). After administration of AAs, the losses increased to 28 +/- 4 g. However, this procedure produced a positive net balance of AAs (10.6 +/- 5.6 g for total AAs), preventing a reduction in plasma concentrations. After 3 mo of AA administration, there was a significant increase in protein catabolic rate and serum albumin and transferrin. This improvement occurred without any change in the dialysis dose, ruling out the possibility that an increase in dialysis efficiency played a role. CONCLUSIONS: Intradialysis adequately provides AA supplements, prevents reductions in plasma AA concentrations, and favorably affects the nutritional status of patients receiving hemodialysis.

Effects of pentoxifylline on the haematologic status in anaemic patients with advanced renal failure.

OBJECTIVE: Erythropoietin (EPO) deficiency is the main cause of renal anaemia. However, inhibition of erythropoiesis by cytokines such as tumour necrosis factor alpha (TNF-a) may play an important role. The aim of this work was to study the effects of pentoxifylline, an agent with anti-TNF-a properties, on the haematologic status in anaemic patients with advanced renal failure. MATERIAL AND METHODS: In a prospective study, 7 anaemic patients with advanced renal disease (creatinine clearance <30 ml/min) were treated with pentoxifylline (400 mg orally daily) for 6 months. The evolution of haemoglobin, haematocrit, creatinine clearance and serum EPO and TNF-a a concentrations were compared with those obtained from an untreated control group. RESULTS: Haemoglobin and haematocrit significantly increased in the pentoxifylline-treated patients (9.9+/-0.5 g/dl and 27.9+/-1.6% at baseline; 10.6+/-0.6 g/dl and 31.3+/-1.9% at the 6th month, respectively, p < 0.01), whereas no variation was seen in the control group. Serum EPO levels remained stable in all patients. However, the serum TNF-a concentration decreased significantly in patients receiving pentoxifylline (basal 623+/-366 pg/ml; 6th month 562+/-358 pg/ml, p < 0.01), but not in the control group. CONCLUSIONS: Our findings suggest that the inhibition of erythropoiesis by cytokines may play a significant role in renal anaemia. The administration of agents with anti-cytokine properties, such as pentoxifylline, can improve the haematologic status in anaemic patients with advanced renal failure.

Autosomal dominant polycystic kidney disease associated with familial sensorineural deafness.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by both renal and non-renal disorders. Extrarenal involvement includes noncystic manifestations such as cardiovascular abnormalities, colonic diverticula and intracranial aneurysms. Familial sensorineural hearing loss (SNHL) has been included in the definition of Alport's syndrome. However, other types of nephropathy have been occasionally associated with hereditary deafness. The association of ADPKD with hereditary SNHL has not been previously documented. We report a family with ADPKD associated with bilateral sensorineural deafness in a pedigree of four affected members in four generations.

Urinary protein excretion and serum tumor necrosis factor in diabetic patients with advanced renal failure: effects of pentoxifylline administration.

In 24 diabetic patients with advanced renal failure (creatinine clearance [C(Cr)] < 35 mL/min), we prospectively studied serum tumor necrosis factor-alpha (TNF-alpha) levels, the possible relationship with urinary protein excretion, and the effects of pentoxifylline (PTF) administration. PTF (400 mg daily) was administered for 6 months to 14 patients, and the results were compared with data from a control group (n = 10). Baseline parameters were similar in both groups. At the end of the study, urinary protein excretion and serum TNF-alpha decreased in the active group from 2.7 (1.2 to 5.8) g/d and 569 +/- 285 pg/mL to 1.1 (0.3 to 4.0) g/d and 329 +/- 232 pg/mL, respectively (P < 0.001). By contrast, proteinuria and TNF-alpha did not change in the control group. Regression analysis showed a significant correlation between proteinuria and serum TNF-alpha both at basal (r = 0.55) and at the sixth month (r = 0.57). Furthermore, the reduction of urinary protein excretion was strongly correlated with the decrease of TNF-alpha (r = 0.72, P < 0.01). Serum Cr and C(Cr) remained stable in both groups during the study. Our findings suggest that cytokines might play a role in renal damage in diabetic nephropathy. PTF is effective in reducing proteinuria in diabetic patients with advanced renal failure. The anticytokine activity of PTF may be a further explanation for this antiproteinuric effect.

Effects of losartan on the treatment of posttransplant erythrocytosis.

Erythrocytosis is a relatively common complication of renal transplantation. Recent observations indicate that angiotensin-converting enzyme inhibitors correct renal transplant erythrocytosis. Other drugs to inhibit the renin-angiotensin system have been developed recently. The newest of these is losartan, a specific antagonist of the angiotensin II type I receptor. We report three patients in which the use of losartan controlled posttransplant erythrocytosis. Our findings suggest that losartan can be effective and safe in the treatment of posttransplant erythrocytosis.

Androgens for the treatment of anemia in peritoneal dialysis patients.

Before the advent of recombinant human erythropoietin (EPO), androgens were used for treatment of anemia in dialysis patients. However, after the availability of recombinant EPO in the 1980s, the use of these substances was abondoned. We have previously reported that androgens have beneficial actions on anemia in selected hemodialysis patients. In the present study we have analyzed the effects of androgen administration on hematologic parameters in peritoneal dialysis patients. We evaluated 9 patients treated for 6 months with nandrolone decanoate (200 mg/week intramuscularly). Hemoglobin and hematocrit values experienced a significant increment with respect to basal values during the study (9.2 +/- 0.7 g/dL and 27.7% +/- 2.3% at basal vs. 11.9 +/- 0.5 g/dL and 35.3% +/- 1.6% at month 6, respectively; P < 0.001). In addition to the effects on the hematologic parameters, androgen administration also had beneficial anabolic actions with a significant increment in the serum concentration of total proteins and albumin (basal, 6.1 +/- 0.3 g/dL and 3.1 +/- 0.4 g/dL vs. 6.7 +/- 0.4 g/dL and 3.8 +/- 0.4 g/dL at month 6, respectively, P < 0.01). The only adverse effect was a rise in the serum concentration of triglycerides (176 +/- 54 mg/dL vs. 144 +/- 53 mg/dL, P < 0.01). In conclusion, androgen administration has beneficial effects on erythropoiesis as well as positive anabolic actions in patients under peritoneal dialysis.

Calcium salts of keto-amino acids, a phosphate binder alternative for patients on CAPD.

Control of hyperphosphoremia is crucial to the prevention of secondary hyperparathyroidism. Calcium salts of keto-amino acids (KAA) were employed as phosphate binders in hemodialysis patients. We wanted to assess the efficacy of these substances as quelating agents in patients under continuous ambulatory peritoneal dialysis (CAPD). Also, as an amino acid supplement, we determined their possible effect on some parameters related to nutritional status. We studied 13 patients (7 M; 6 F) with a mean age of 45.2 +/- 17 years and a mean time on CAPD of 18.4 +/- 11.4 months. None had severe secondary hyperparathyroidism and/or clinically relevant aluminium intoxication. They were not receiving calcitriol and none were using low-calcium peritoneal dialysis fluids. All were under aluminum hydroxide (AlOH3) treatment and 8 patients also received calcium carbonate. These quelating agents were withdrawn and after 21 days (wash-out period) KAA were initiated. We analyzed serum levels of bone metabolism parameters (calcium, phosphate, osteocalcin [OC], intact parathyroid hormone [iPTH], alkaline phosphatase [AP]) and nutritional parameters (total protein, albumin, pre-albumin, transferrin) in four periods: (A) during AlOH3; (B) immediately after the washout period; (C) after 1.5 months; and (D) after 3 months of KAA therapy. In 5 patients serum aluminum level was also measured in periods (A) and (D). The serum phosphate level at period (B) was significantly higher than in other periods. After 3 months of treatment phosphate levels decreased significantly (A = 1.77 +/- 0.3 mmol/l vs D = 1.48 +/- 0.2; p < 0.05). Serum calcium levels increased, while iPTH and OC decreased (p = ns). AP remained stable during the study. All nutritional parameters increased at the end of the study (p = ns). Calcium salts of keto-amino acids showed to be an effective alternative to aluminum-containing phosphate binders. They were well tolerated, without relevant side-effects. These compounds could also represent an additional source of oral amino acid supplementation with improvement of nutritional status.

Serum magnesium concentration and PTH levels. Is long-term chronic hypermagnesemia a risk factor for adynamic bone disease?

The observation that some subjects with low PTH had elevated plasma magnesium (Mg) levels prompted us to analyze in 41 patients on maintenance hemodialysis for 44 +/- 36 months, their serum Mg concentrations, and the relationship between plasma Mg and PTH levels. The mean serum Mg concentration was 2.4 +/- 0.2 mg/dl. Twenty-four out of the 41 subjects (58.5%) had hypermagnesemia (serum Mg above 2.5 mg/dl). Patients were classified into 3 groups according to their PTH level: Group A, low PTH (below 120 pg/ml); group B, adequate PTH (120-250 pg/ml); and group C, high PTH (above 250 pg/ml). There were no differences among groups according to number of subjects, age, sex, time on dialysis, renal disease, serum calcium, phosphorus, bicarbonate, vitamin D or aluminum concentrations. Doses of calcium carbonate and aluminium hydroxide were also similar in all groups. Curiously, although the differences were not statistically significant, the total cumulative intake of calcium and aluminium were less in group A than in the other groups. Interestingly, patients with low PTH had a significantly higher serum Mg concentration than patients with adequate or high PTH (2.8 +/- 0.2 mg/dl vs 2.3 +/- 0.1 mg/dl and 2.2 +/- 0.1 mg/dl, respectively, p < 0.01). Moreover, regression analysis showed a negative linear correlation between serum PTH level and plasma Mg concentration (r = -0.6059, p < 0.001). Based on these findings, chronic hypermagnesemia could have a suppressive effect on PTH secretion, and it could be a risk factor for the development of adynamic bone disease in dialysis patients.

Hemodialysis urea rebound and membrane biocompatibility: accuracy of Kt/V estimations.

To date, the magnitude, causes, and factors that govern urea rebound are not clearly defined. This study was undertaken to determine the possible influence of the biocompatibility of dialyzer membrane on urea rebound and to assess the participation of rebound in the calculation of Kt/V-urea by different methods. Blood urea samples were obtained before, and at 2, 30, and 60 min posthemodialysis in 8 patients undergoing dialysis with 2 different membranes, Cuprophan and polyacrylonitrile (24 sessions with each membrane). Urea rebound was documented in all patients. The degree of rebound was large, 20%, and it was achieved within 30 min after the end of dialysis. Urea rebound was observed with both Cuprophan and polyacrylonitrile membranes, without significant differences. Kt/V-urea significantly decreased (p < 0.001) by all methods when urea rebound was incorporated. We conclude that urea rebound is clinically very important and is not influenced by the biocompatibility of the dialyzer membrane. This phenomenon must be taken into account in the calculation of Kt/V; otherwise, it might be overestimated.

Effects of angiotensin-converting enzyme inhibitors on anemia and erythropoietin requirements in peritoneal dialysis patients.

In an attempt to assess the effect of angiotensin-converting enzyme inhibitors (ACEIs) on anemia and recombinant human erythropoietin (rHuEPO) requirements in peritoneal dialysis patients, we evaluated 5 patients treated with ACEIs for one year, and the results were compared with data from a control group (N = 5). In response to ACEIs, the mean hemoglobin value decreased progressively, reaching statistical significance after 6 months and thereafter (basal, 10.7 +/- 0.8; month 6, 10.3 +/- 0.9; month 12, 10.3 +/- 0.5 g/dL, p < 0.05), with no variations in the control group. The rHuEPO requirements experienced a progressive increase in ACEI-treated patients, from 4400 +/- 1516 U/week at basal to 8600 +/- 2880 U/week at the conclusion of the study (p < 0.01). Serum erythropoietin concentration remained stable during the study in both groups of patients. In conclusion, rHuEPO requirements necessary to maintain a stable hemoglobin concentration are greater in subjects under ACEI therapy. ACEI may be an important cause of resistance to rHuEPO, an effect not mediated by a decrease in endogenous erythropoietin.

[Late hereditary degenerative sensorineural hearing loss associated with IgA mesangial glomerulonephritis of probable autosomal dominant heredity]. / Hipoacusia neurosensorial heredodegenerativa tardía, asociada a glomerulonefritis mesangial IgA, de probable herencia autosómica dominante.

We studied four generations of a Canary Islands family presenting a tardive heredodegenerative hearing loss, associated with IgA mesangial glomerulonephritis, of probable autosomal dominant heredity. With respect to the family, we revised Alport's syndrome, for possible transmission associated with X chromosome, as well as heredodegenerative hearing loss associated with renal pathology of autosomic transmission currently described; we differentiate these hearing losses from our case study, and we discuss the pathogeny of the auditive affection in the said hereditary syndromes. Lastly, we stress the autoimmune hypothesis because of the IgA nephropathy association in the family case, and we list the characteristics of the syndrome described.

Familial IgA nephropathy associated with bilateral sensorineural deafness.

Alport's syndrome is the most frequent disorder with familial nephritis and deafness, but other types of nephropathy have been occasionally associated with hereditary hearing loss. The familial occurrence of IgA nephropathy has been well documented. We report a family with hereditary, bilateral, sensorineural deafness spanning four generations. Three of five members with deafness had microscopic hematuria. Renal histology of the two deaf members undergoing biopsy showed mesangial glomerulonephritis with mesangial IgA deposits, without ultrastructural abnormalities of the glomerular basement membranes. Familial nephritis with deafness should not be equated with the diagnosis of Alport's syndrome.