Pieter F. Vos

Conversion from Cyclosporine to Tacrolimus Improves Quality of Life Indices, Renal Graft Function and Cardiovascular Risk Profile

Long‐term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived side‐effects were investigated after a follow‐up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 ± 48 μmol/L to 157 ± 62 μmol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 ± 4.3 to 4.8 ± 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side‐effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side‐effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long‐term treatment with a calcineurin inhibitor is indicated.

Improved Cardiovascular Risk Profile and Renal Function in Renal Transplant Patients after Randomized Conversion from Cyclosporine to Tacrolimus

Cyclosporine is considered to contribute to the high cardiovascular morbidity and mortality in patients after renal transplantation. Tacrolimus may be more favorable in this respect, but controlled data are scarce. In this prospective randomized study in 124 stable renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on cardiovascular risk factors and renal function were investigated. Follow-up was 6 mo. Statistical analysis was performed by ANOVA for repeated measurements. The serum creatinine level decreased from 137 +/- 30 micromol/L to 131 +/- 29 micromol/L (P < 0.01). Three months after conversion from cyclosporine to tacrolimus, mean BP significantly decreased from 104 +/- 13 to 99 +/- 12 mmHg (P < 0.001). Serum LDL cholesterol decreased from 3.48 +/- 0.80 to 3.11 +/- 0.74 mmol/L (P < 0.001,) and serum apolipoprotein B decreased from 1018 +/- 189 to 935 +/- 174 mg/L (P < 0.001). Serum triglycerides decreased from 2.11 +/- 1.12 to 1.72 +/- 0.94 mmol/L (P < 0.001). In addition, both rate and extent of LDL oxidation were reduced. The fibrinogen level decreased from 3638 +/- 857 to 3417 +/- 751 mg/L (P < 0.05). Plasma homocysteine concentration did not change. Three months after conversion, plasma fasting glucose level temporarily increased from 5.4 +/- 1.3 mmol/L to 5.8 +/- 1.9 mmol/L (P < 0.05). Conversion to tacrolimus resulted in a significant reduction of the Framingham risk score. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients has a beneficial effect on renal function, BP, serum concentration and atherogenic properties of serum lipids, and fibrinogen.

Sympathetic hyperactivity in haemodialysis patients is reduced by short daily haemodialysis.

Objective Haemodialysis patients often have sympathetic hyperactivity. The hypothesis of this study was that a switch from three times weekly to short daily dialysis could affect sympathetic hyperactivity. Methods We studied 11 patients (eight men; aged 46 ± 8 years) stable on haemodialysis for at least 1 year before and 6 months after conversion from three times to six times weekly dialysis without increasing total dialysis time (short daily dialysis). Seven patients were restudied 2 months after switching back to three times weekly haemodialysis. Results Ultrafiltration volume per session decreased from 2.4 ± 1.0 to 1.5 ± 0.6 l (P < 0.05). The extracellular fluid volume (bromide distribution space) did not change. Mean arterial pressure (without medication) decreased from 113 ± 11 to 98 ± 9 mmHg (P < 0.05). Cardiac output (Doppler echocardiography) did not change, but peripheral vascular resistance decreased from 25.4 ± 6.4 to 21.2 ± 3.2 mmHg per min/l (P < 0.05), in conjunction with a decrease in muscle sympathetic nerve activity (MSNA) from 39 ± 19 to 28 ± 15 bursts/min (P < 0.05). Ambulant 24 h blood pressure decreased and the nocturnal blood pressure dip increased during short daily dialysis. The seven patients who were switched back to alternate day haemodialysis showed a return of the high MSNA and peripheral vascular resistance. Conclusion The study shows that sympathetic hyperactivity in haemodialysis patients is reduced by increasing the frequency of treatment sessions. This is probably because of the decrease in number or magnitude of the fluid fluctuations.

The management of xerostomia in patients on haemodialysis: comparison of artificial saliva and chewing gum

Many patients on haemodialysis (HD) therapy suffer from a dry mouth and xerostomia. This can be relieved by mechanical and gustatory stimulation or palliative care. The aim of this crossover study was to investigate the effect and preferences of a sugar-free chewing gum (Freedent WhiteTM) and a xanthan gum-based artificial saliva (XialineTM) in the management of xerostomia in chronic HD patients. Sixty-five HD patients participated in a 6-week crossover trial. The artificial saliva was rated significantly lower than the chewing gum for effectiveness, taste and a global assessment. No preference differences were found for gender and age, although older subjects rated the artificial saliva with a higher mark. Thirty-nine subjects (60%) preferred chewing gum, 15% (n = 10) preferred the artificial saliva. Therefore, both chewing gum and artificial saliva could play an important role in the palliative care of xerostomia in HD patients.

Acute effects of hemodialysis on salivary flow rate and composition.

AIMS To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session. MATERIAL AND METHODS Unstimulated whole saliva (UWS) and chewing-stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH, concentrations of total protein, albumin, cystatin C, secretory immunoglobulin A (S-IgA) and of sodium, potassium and urea were measured. RESULTS HD had an acute stimulating effect on the salivary flow rate (UWSbefore = 0.30+/-0.22 ml/min, UWSduring = 0.39+/-0.25 ml/min, p < 0.005). The mean pH of UWS showed a small but significant increase during HD mainly due to an increased watery secretion from the salivary glands. The salivary biochemical constituents changed markedly, but no significant difference in output was found. The electrolyte concentration did not change significantly during dialysis. The level of urea in CH-SWS declined to 40% (Ureabefore = 25.+/-6.4 mmol/l, Ureaduring = 15.3+/-4.5 mmol/1). CONCLUSIONS This study shows that HD has significant acute effects on both salivary secretion rate and protein concentrations in saliva. We conclude that the observed changes in salivary concentrations and proteins are mainly due to an increased watery secretion from the salivary glands.

Daily Home Hemodialysis: Towards a More Physiological Treatment of Patients with ESRD

A major task of the kidney is to maintain homeostasis. Renal regulatory mechanisms are continuous, not intermittent, resulting in a constant biochemical composition of the extracellular fluid and a constant control of body water volume, within narrow limits. A healthy person is not overhydrated and dehydrated or hyperkalemic and hypokalemic twice or thrice weekly, and most physicians will agree that the maintenance of the many physiological parameters at an optimal level is a prerequisite for health. However, the same physicians, while treating hemodialysis patients, seem to be satisfied with a highly unphysiological therapy that combines low adequacy with intermittent and infrequent control of volume and biochemical composition of the extracellular fluid. Currently, most hemodialysis patients are still exposed to the so-called “unphysiology” of dialysis, a concept which was described almost 25 years ago (1). In searching for more physiological hemodialysis treatment schedules, the aspect of adequacy of solute removal has earned much attention, and data suggesting an inverse relationship between adequacy and mortality culminated in the NKF-DOQI guidelines (2). However, an “adequate” dialysis dose delivered thrice weekly, resulting in large biochemical and body fluid volume fluctuations with potentially hazardous peaks and troughs, is still highly unphysiological. More frequent dialysis schedules may better mimic the normal physiological situation, and a growing body of evidence supports this statement. One of these schedules is short daily home hemodialysis (DHHD).