The importance of body composition and dry weight assessments in patients with chronic kidney disease.

Chronic volume overload is the major cause of hypertension and other cardiovascular morbidity in dialysis patients. One of the most important goals of physicians who take care of patients with chronic renal failure is to obtain near euvolemia or "dry body weight" in order to maintain or normalize blood pressure and prevent further cardiovascular events. In clinical practice, exact estimation of dry weight in hemodialysis patients remains a major challenge. Alterations in body composition, particularly malnutrition, are common in patients receiving long-term hemodialysis and contribute to a high mortality rate. In contrast, obesity - a known risk factor for cardiovascular morbidity and mortality - is prevalent amongst kidney allograft recipients in - long term after renal transplantation. Several technological tools and biochemical markers for estimation of plasma volume and body composition are available for clinical use. Our aim was to highlight the importance of control of body fluid volume and body composition in patients with chronic kidney disease and to describe the different methods available for such measurements.

Diurnal blood pressure variations in incipient and end stage diabetic renal disease.

Our aim was to compare the diurnal blood pressure patterns of people with Type 1 diabetes on continuous ambulatory peritoneal dialysis (CAPD, n=9) or haemodialysis (n=10) to diabetic patients with normo-albuminuria (n=12) or micro-albuminuria (n=15). Blood pressure was measured with an ABPM02 Meditech oscillometric blood pressure monitor. The micro-albuminuric group had significantly higher nocturnal diastolic and mean arterial pressures than the normo-albuminuric group. CAPD and haemodialysis patients had significantly higher day time, nocturnal mean systolic, diastolic and mean arterial blood pressures. Micro-albuminuric and end-stage renal failure patients displayed a loss of the physiological drop of systolic blood pressure, which was only significant in the normo-albuminuric group. Nocturnal drop of blood pressure characterised by diurnal indices were 7.4% in the CAPD, 8.8% in the haemodialysis, 10.0% in the micro-albuminuric and 16.5% in the normo-albuminuric group. These results suggest, that pathological circadian blood pressure variation is common in diabetic patients on dialysis, and ambulatory blood pressure monitoring can be a useful tool both in its the detection and its adequate treatment.

Can sterile and pyrogen-free on-line substitution fluid be routinely delivered? A multicentric study on the microbiological safety of on-line haemodiafiltration.

BACKGROUND: Microbial contamination is characterized not only by the presence of bacteria, but also by high concentrations of biologically active by-products. They are potentially able to cross ultrafiltration and dialysis membranes and stimulate immunocompetent blood cells to synthesize cytokines. In turn, cytokine induction causes acute symptoms and has been incriminated in the long-term complications of haemodialysis patients. Infusion of large volumes of substitution fluids following ultrafiltration of microbially contaminated dialysis fluids may place patients on on-line therapies at particular risk. METHODS: In this study we evaluated 30 machines with a two-stage ultrafiltration system in routine clinical haemodiafiltration settings in six centres for 6 months. Microbiological safety was assessed monthly and at the last use of the filters by determining microbial counts, endotoxin concentration and cytokine-inducing activity. RESULTS: No pyrogenic episodes were observed during the study period. Double-filtration of standard dialysis fluid (range, <1-895 cfu/ml, 0.0028-4.6822 IU/ml) resulted in sterile substitution fluids with endotoxin concentrations well below the Ph.Eur. standard for haemofiltration solutions (range, 0.0014-0.0281 vs 0.25 IU/ml). Moreover, they did not differ from commercial haemofiltration solutions and depyrogenated saline. Likewise, there was no difference in the cytokine-inducing activity between the solutions tested. The high microbiological quality of the ultrafiltered dialysis fluid, which was in the same range as substitution fluid, translates into both the absence of cytokine induction by dialyser back-transport and a redundant safety mode of the on-line system by a second filtration step. CONCLUSION: On-line HDF treatment can routinely be provided with ultra-pure dialysis fluids and sterile substitution fluids at pyrogen-free levels. The online preparation of substitution fluids thus can be considered microbiologically safe.

Albuminuria after fetal pancreatic islet transplantation: a 10-year follow-up.

AIM OF THE STUDY: The prevention of diabetic nephropathy is as yet an unresolved issue. The aim of our study was to assess the effects of transplantation of long-term cultured and cryopreserved fetal pancreas islets on metabolic control and the development of diabetic nephropathy. METHODS: Serum C-peptide, glucose, HbA1c, insulin requirements, urinary albumin excretion rate, and blood pressure of 10 insulin-dependent diabetic patients after transplantation were compared with a group of 27 insulin-dependent diabetic controls on insulin therapy only during a 10-year follow-up. RESULTS: In the first year after transplantation mean insulin requirement decreased from 53.6+/-2.2 to 35.8+/-1.2 units. C-peptide levels appeared (0.55+/-0.08 ng/ml) and remained detectable throughout the follow-up. Blood glucose and HbA1c were significantly (P<0.05) lower than in the controls. Mean albumin excretion rates of the transplant and the control groups during the follow up were 18.8+/-8.5 and 11.7+/-2.0, 16.6+/-6.6 and 14.0+/-2.3, 15.0+/-5.0 and 15.1+/-2.7, 15.3+/-7.5 and 20.4+/-4.2, 19.8+/-6.2 and 36.7+/-11.1, 11.7+/-3.6 and 51.3+/-14.6, 14.1+/-4.2 and 71.4+/-23.1, 22.7+/-8.6 and 92.0+/-28.1, 18.0+/-5.9 and 107.6+/-35.6, 21.7+/-11.0 and 101.5+/-29.3 microg/min respectively. From the 6th year the difference between the two groups was significant (P<0.001). In the transplant group initial mean systolic and diastolic blood pressure values were 132.0+/-3.3 and 81.5+/-1.5 mmHg, in the controls 130.4+/-3.4 and 79.6+/-1.6 mmHg respectively. Significant changes (P<0.05) of blood pressure during the follow-up or differences between the two groups were not observed. CONCLUSIONS: We conclude that fetal islet transplantation is effective in achieving good long-term diabetes control and in the prevention of diabetic nephropathy.

Diurnal blood pressure variation and albuminuria in normotensive patients with insulin-dependent diabetes mellitus.

BACKGROUND: Abnormalities of the systemic blood pressure are closely associated with the development of diabetic nephropathy. Our aim was to examine the relationship between diurnal blood pressure pattern and albuminuria in insulin-dependent normotensive diabetic patients before the development of overt nephropathy. METHODS: Urinary albumin excretion rates were determined by radioimmunoassay, and 24-h ambulatory blood pressure monitoring was performed. Means and diurnal index was calculated for systolic, diastolic and mean arterial blood pressure, for day-time, night-time, and the whole day. The results of the normoalbuminuric (n = 39) and microalbuminuric (n = 29) groups are compared, and correlation of the blood pressure parameters with albuminuria is analysed. RESULTS: Twenty-four hours and night-time mean blood pressures were significantly higher, diurnal indices characterizing the night-time blood pressure drop were smaller in the microalbuminuric group. With multiple regression analysis a significant positive correlation was found between albumin excretion rates and 24-h mean systolic blood pressure and a significant negative correlation between albumin excretion rates and the diurnal index of mean arterial pressure (r2= 0.40, P<0.0001). In the normoalbuminuric group 1 (2.6%) patient, in the microalbuminuric group 7 (24.1%/) were 'non-dippers'. CONCLUSION: We conclude that in normotensive insulin-dependent diabetic patients the night-time decrease of blood pressure is smaller if microalbuminuria is present. Higher nocturnal blood pressure load is associated with the increase of albuminuria, even before the onset of overt diabetic nephropathy or hypertension.

A strategy for informing patients and health professionals about unconventional cancer therapies.

BACKGROUND: A Guide to Unconventional Cancer Therapies was produced by the Ontario Breast Cancer Information Exchange Project with the intention of meeting needs of patients, family members, and health professionals for information about unconventional therapies. Concerns raised by health professionals during the development of the guide serve as a focus for considering its impact on cancer patients who purchased it. MATERIALS AND METHODS: Purchasers of the guide were sent a survey questionnaire inquiring about their access to, use of, and attitudes toward it. RESULTS: A total of 634 individuals responded to the survey, including cancer patients, health professionals, and family members. The guide was rated moderately helpful overall, and health professionals found it significantly more helpful than did cancer patients. A minority of patients were influenced to try an unconventional therapy as a result of reading the guide. Those who did try a new therapy typically chose ones that are most popular and have few potential negative effects. CONCLUSIONS: As an informational strategy, the Guide to Unconventional Cancer Therapies has been successful. Concerns expressed by some health professionals about potential harm through implementing the strategy have been shown to be largely unwarranted, at least for study respondents.

The efficacy of long-term captopril treatment on micro- and macroalbuminuria in hypertensive diabetics.

Microalbuminuric [16] and macroalbuminuric [17] hypertensive insulin dependent diabetics were followed up for 4 years after the initiation of captopril therapy to assess the efficacy of ACE inhibitor therapy on albuminuria and blood pressure normalisation. Within the first six months of captopril therapy mean systolic blood pressure decreased in microalbuminuric and macroalbuminuric patients from 168.1 +/- 17.6 mmHg to 134.4 +/- 12.1 mmHg (19.2 +/- 7.1%) and from 177.6 +/- 16.8 mmHg to 143.5 +/- 12.7 (18.9 +/- 6.7%) mmHg, respectively. Mean diastolic blood pressure, similarly, showed a decrease from 91.9 +/- 9.1 mmHg to 74.4 +/- 10.3 mmHg (19.0 +/- 9.4%) in the microalbuminuric and from 95.3 +/- 13.7 mmHg to 78.2 +/- 7.3 (16.9 +/- 9.5%) mmHg in the macroalbuminuric group. After six months of captopril administration albumin excretion rates decreased as well, from 97.4 +/- 35.9 micrograms/min to 51.9 +/- 19.9 micrograms/min (46.9 +/- 7.6%) and from 766.7 +/- 577.9 micrograms/min to 365.1 +/- 298.4 micrograms/min (50.4 +/- 8.4%) in the micro- and macroalbuminuric groups, respectively. Thereafter, mean albumin excretion rates and blood pressure rose significantly, but at the end of the fourth year they were still significantly lower compared to that of the pretreatment period. After four years, albumin excretion rates were 71.3 +/- 29.6 micrograms/min in the microalbuminuric and 391.2 +/- 204.7 micrograms/min in the macroalbuminuric group. We conclude that ACE inhibitor therapy results in a rapid decrease of albuminuria and blood pressure, and despite a slow gradual increase, the albumin excretion rates and blood pressure values remain significantly lower than the initial values after four years.

[Study of 24-hour changes in blood pressure in various stages of diabetic nephropathy]. / A 24 órás vérnyomásváltozások vizsgálata a diabeteses nephropathia különbözö stádiumaiban.

The aim of the study was to compare the diurnal pattern of blood pressure in diabetic patients with normal urinary protein excretion, microalbuminuria and end stage renal failure due to diabetic nephropathy and on continuous ambulatory peritoneál dialysis. An ABPM-oscillometric blood pressure monitor was used. Cholesterol, triglicerides, HDL and LDH1 cholesterole, apolipoprotein A1 and B, endogenous creatinine urinary protein and albumin excretion, beta-2-microglobulin were measured. The mean age and the mean diabetes duration of the 12 normoalbuminuric patients 38.3 and 16.5 years, of the 12 patients treated for renal failure with continuous ambulatory peritoneál dialysis 54.4 and 19.5 years. In the group with end stage renal failure and continuous ambulatory peritoneál dialysis, the mean nocturnal and diurnal systolic and diastolic blood pressure and the average arterial mean pressure was significantly higher than in the normal and microalbuminuric groups. In microalbuminuric and dialysed patients the physiological nocturnal decline of arterial blood pressure was absent. 24 hour blood pressure monitoring may accurately identify the early stage of diabetic nephropathy, and it might be valuable in the correction of antihypertensive treatment from the early to the final stages of diabetic nephropathy.

Physician perspectives on unconventional cancer therapies.

The popularity of unconventional therapies has grown dramatically in recent years. This paper reports on the results of a pilot study investigating the perspectives of physicians involved with cancer care regarding their reactions to this trend and their ways of trying to meet associated challenges. Nine oncologists, nine general practitioners, and one surgeon were interviewed over the telephone, employing open-ended questions. The physicians were unanimously interested in having information available about unconventional therapies. They also expressed a desire to be supportive of patient choices in this area, provided conventional therapy was not compromised. However, there was little interest in initiating communication about unconventional therapies, with most seeing such discussions as a poor use of their time. Suggestions for future research, as well as educational and policy strategies, are addressed.

Successful simultaneous transplantation of kidney and fetal pancreatic islet masses.

This paper reports our experience with the successful simultaneous transplantation of kidney and fetal pancreatic islets in 46-year-old diabetic man. No detectable C-peptide level was noted and the end-stage nephropathy required hemodialysis. The cadaver kidney and two masses of 8-week-cultured fetal islets were grafted simultaneously. After revascularization of the kidney, the islet masses were placed under the kidney capsule. Following transplantation, islet function was demonstrated by a higher C-peptide level, which subsequently persisted. Twenty-four months after grafting, islet function was provoked by glucagon and glucose, which led to elevations in the C-peptide and insulin levels. The insulin requirement fell from 58 to 24 U/day during the post-transplant period of 24 months. The mean value of HbA1C (5.6% +/- 0.3%) indicated a constantly normal carbohydrate metabolism. Improvements in retinopathy were also noted. Three periods of kidney rejection were diagnosed, but these proved reversible with high-dose steroid treatment. The serum and urine beta-2-microglobulin levels correlated well with rejection and recovery. More than 2 years after grafting, kidney functions is in the normal range. On sonography, the transplanted islet masses were repeatedly clearly visible, and 24 months following transplantation the volume was twice the original one. The results indicate that simultaneous kidney and fetal pancreatic islet grafting is advantageous in end-stage nephropathy secondary to type I diabetes mellitus.

[In vitro study and clinical transplantation of human fetal islands of Langerhans]. / Humán fetális Langerhans szigetek in vitro vizsgálata és klinikai transzplantációja.

A simple and reliable procedure was developed for the long-term culturing and cryopreservation of human fetal pancreatic islets. The methods involved can ensure the survival and the growth capacity of fetal tissue. The long-term cultivation or cryoculturing of fetal islet tissue was applied in 23 clinical transplantatious on the basis of the experimental study. All of the diabetic patients suffered progressive retinopathy and three of them had nephropathy as well. After grafting the insulin requirement reduced significantly (39.4%) correlated with the higher serum C-peptide level (mean: 0.41 ng/ml). During the long-term follow-up (9 yrs), the graft function failed in 5 cases, while in 18 successful cases the long term graft function depended on the volume of the grafted islet mass. The results suggest that the transplantation of fetal pancreatic islet has a beneficial effect in the early stage of diabetic complications.

[Relationship between platelet hyperactivation and dyslipoproteinemia in diabetic nephropathy]. / A diabeteses nephropathiát kísérö dyslipoproteinaemia és a thrombocyta aktiváció összefüggése.

The relationship between the secundaer hyperlipidaemia and pathological platelet activation was examined in 40 insulin-treated diabetic patients without nephropathy and 21 with nephropathy. Diabetic nephropathy was recorded with the measurements of serum creatinine, serum beta 2-microglobulin, and urine albumin excretion. Haemostasis and lipoprotein metabolism were characterized with determination of platelet aggregation, plasma beta thromboglobulin, thromboxane-B2, serum triglyceride, HDL and LDL cholesterol concentration, respectively. In the normalbuminuric group serum triglyceride and thromboxane-B2 positively correlated. In the nephropathic group serum cholesterol and beta thromboglobulin, as well as LDL and beta thromboglobulin, finally, LDL and thromboxane-B2 showed significant positive correlation. In diabetic patients without nephropathy platelet aggregate ratio was in positive correlation with the serum triglyceride, while the ED50-S elevated with the increase of serum cholesterol and LDL. The nephropathic group exhibited no such parallelisms. However, there were significant correlations of LDL with serum creatinine in both groups of diabetic patients. Our results seem to indicate that the increase of LDL could be associated with the change of LDL structure. Interactions of modified LDL and the platelet membrane might contribute to the platelet hyperactivation both in the nephropathy-free and nephropathic cases.

[Prospective study of cardiac autonomic neuropathy in diabetes mellitus]. / Kardiális autonom neuropathia prospektív vizsgálata diabetes mellitusban.

For assessment of clinical and prognostic values of cardiac autonomic neuropathy, 53 patients with diabetes mellitus were followed-up for five years. Parasympathetic innervation was assessed by recording heart rate variability during deep breathing, Valsalva manoeuvre and lying-to-standing while sympathetic function was evaluated by measuring postural change in systolic blood pressure. During the follow-up period 1 of 23 diabetic patients died in group without signs of cardiac autonomic neuropathy whereas 2 of 13 diabetics and 10 of 17 diabetics deceased in groups with mild and definitive signs of cardiac autonomic neuropathy, respectively. At reinvestigation, the values of tests for parasympathetic impairment worsened or did not change significantly while improvement in these tests was only exceptionally observed in 40 diabetic patients. No significant change in values of test for sympathetic function was documented during the follow-up period suggesting that parasympathetic (vagal) impairment might precede the sympathetic dysfunction during development of autonomic neuropathy in diabetic patients. No correlation was observed between changes in cardiac autonomic neuropathy and alterations in distal somatic neuropathy (assessed by measurement of motor nerve conduction velocity in peroneal nerves) during the prospective study. Definitive cardiac autonomic neuropathy--as one of the late complications of diabetes mellitus--suggests poor prognosis in diabetic patients.

Cardiac autonomic neuropathy and QT interval length. A follow-up study in diabetic patients.

For evaluating the clinical significance of QT interval prolongation in diabetics with cardiac autonomic neuropathy (CAN), 53 diabetic patients were followed-up for 5 years or to death and the results of cardiovascular function tests as well as the values of QT intervals were repeatedly determined. At baseline investigation, the QTc intervals were significantly longer in diabetics with definitive (456 +/- 5 ms, mean +/- SEM, n = 17) than those with early (435 +/- 5 ms, n = 13, p less than 0.01) and without (413 +/- 4 ms, n = 23, p less than 0.001) signs of CAN or in controls (414 +/- 5 ms, n = 15, p less than 0.001). Thirteen patients died during the follow-up period (1 without, 2 with early and 10 with definitive signs of CAN) but QTc intervals did not differ significantly between patients with cardiac (456 +/- 9 ms, n = 8) and non-cardiac (459 +/- 15 ms, n = 5) causes of death. At reinvestigation of 40 patients, the severity of CAN worsened in 22 patients, remained unchanged in 15 patients and improved in 3 patients. Accordingly, the mean values of autonomic function tests decreased (beat-to-beat variation from 15 +/- 2 to 9 +/- 1 beats/min, p less than 0.01; 30:15 ratio from 1.19 +/- 0.03 to 1.09 +/- 0.02, p less than 0.01) while QTc interval increased (from 424 +/- 3 to 431 +/- 4 ms, p less than 0.01). It was concluded that CAN carries a poor prognosis in diabetic patients. Nevertheless, QTc interval prolongation could be evaluated as rather an additional sign of CAN than the only explanation for mechanism in the pathogenesis of sudden cardiac death in diabetic patients.