Could depression be a new branch of MIA syndrome?

The aims of the present study were to determine the prevalence of depression in our dialysis patients, to detect the most powerful variables associated with depression, and to determine the role of depression in prediction of mortality. The prospective follow-up study of 128 patients (77 HD and 51 CAPD, 65 male, aged 53.8 +/- 13.5 years, dialysis duration 64.7 +/- 64.8 months) was carried out over 36 months. Depression by the Beck Depression Inventory-BDI-II score, laboratory parameters (hemoglobin, serum albumin and creatinine concentration), immunological status (cytokines and hsCRP), comorbidity by Index of Physical Impairment (IPI) and adequacy of dialysis by Kt/V were monitored. The overall prevalence of depression in the dialysis patients (BDI score > or = 14) was 45.3%, and 28.2%, respectively, for moderate and severe depression (BDI > or = 20). The most powerful variable associated with depression was IL-6, but associations with albumin, hemoglobin, creatinine and IPI score were also found. During the follow-up period 36 patients died, 7 patients left the cohort and 2 patients were transplanted. If IPI score was not included in the multivariate Cox analysis, the BDI score remained one of the best predictors of mortality along with albumin. In conclusion, because of the close association of depression with inflammation, malnutrition, and cardiovascular mortality, it could be speculated that depression is one branch of the MIA (malnutrition, inflammation, atherosclerosis) syndrome.

Hemodialysis modality, percentage of body fat, and patient survival.

BACKGROUND: A number of studies have reported lower mortality of overweight hemodialysis patients. This post hoc analysis of an observational prospective single-center study was aimed at elucidating whether both being overweight and surviving longer could result from changes in the hemodialysis modality. METHODS: The study included a cohort of 242 patients who were gradually switched from cuprophane membrane and acetate dialysis to polysulfone (including high-flux) membranes and bicarbonate dialysis. The analysis involved 12 months of baseline data obtained during the first calendar year after the patients entered the study (1994-2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and the percentage of body fat (%fat) was calculated from triceps, biceps, subscapular, and suprailiac skinfolds (K/DOQI guidelines).Kt/V, normalized protein catabolic rate, and cardiovascular comorbidity were also determined and laboratory analyses undertaken. RESULTS: Significant correlations were found between %fat and bicarbonate dialysate as well as polysulfone membrane and high-flux membrane. The linear mixed model showed dependence of %fat on polysulfone and high-flux membrane (p<0.01) Multivariate Cox regression (time-dependent covariates) found %fat to be an independent factor for longer survival, in addition to polysulfone and high-flux membranes. CONCLUSION: Changes in hemodialysis modality were followed by both higher body fat percentage and patient survival. The reverse epidemiology of overweight patients might be at least partially the result of the influence of nonnutritional factors, such as a change in hemodialysis modality (introducing biocompatible high-flux and low-flux membranes and bicarbonate dialysis).

Relation between serum urea and mortality of hemodialysis patients.

BACKGROUND: It is well known that serum urea concentration is not a good predictor of mortality in hemodialysis patients. On the other hand, urea kinetic modeling has been very successfully used to measure dialysis dose by the Kt/V index, which was found to be a good predictor of mortality. Could there be a relation between urea and mortality, but in some more complex way? METHODS: This is a post-hoc analysis of a single center observation study that included 242 patients and an 11-year observation period. Mortality rates between the quartiles of serum urea levels were examined by a 2 x 4 table with the chi(2) test. Both univariate and multivariate survival analyses were performed with standard and segmented extended Cox regression. RESULTS: The relation between mean urea in the baseline period and mortality showed an irregular U-shaped curve. The lowest mortality was observed in the third quartile (28 to 31 mmol/L). The relation between mean urea in the whole observation period and mortality was a J-shaped curve. The lowest mortality was in the second quartile (25-27 mmol/L). Urea was not a predictor of mortality in the whole cohort, but low-urea (binary) and high-urea (binary) were independent predictors of mortality in the corresponding models using standard or extended Cox regression. CONCLUSION: This study revealed a complex relationship between urea and mortality in hemodialysis patients. Patients with low or high urea levels exhibited higher mortality than those with medium levels, while both low and high levels of urea were independent predictors of all-cause mortality.

Heart and renal failure in renovascular hypertension caused by giant cell arteritis--case report.

We report a case of a male teenager with severe heart and acute renal failure as the dominant clinical manifestations of renovascular hypertension (RVH) caused by atypical giant cell arteritis (GCA). Unrecognized RVH and treatment of the consequent heart failure by angiotensin-converting enzyme inhibitors (ACEI) probably contributed to progression of renovascular disease to bilateral renal artery occlusion. Recurrent "flash" pulmonary edemas could not be prevented until surgical revascularization of the only functioning right kidney was achieved by an aortorenal bypass. Prompt post-operative normalization of heart function and arterial hypertension occurred despite the histopathological finding of the resected renal artery compatible with GCA and 4-year duration of significant renovascular disease. At the last check-up, the patient was asymptomatic, with normal arterial pressure on the prescribed treatment: carvedilol, hydrochlorothiazide, prednisolone 20 mg daily and aspirin. Subsequent follow-up is necessary to observe the evolution of GCA as an exceptionally rare cause of RVH.

Fuzzy role of hyperhomocysteinemia in hemodialysis patients' mortality.

Recent studies give contradictory data regarding the role of hyperhomocysteinemia (hyperHcy) in cardiovascular (CV) morbidity and mortality in hemodialysis (HD) patients. The aims of the present study were to detect the most powerful variables associated with hyperHcy as well as to evaluate the relationship between hyperHcy and CV morbidity and mortality. The prospective follow-up study of 113 patients (52 males, aged 55.2+/-13.1 years) maintained by HD for 81.9+/-56.9 months at our Institute was carried out over 55 months. Fifty-seven (50.4%) of the examined patients were supplemented with water-soluble vitamins including folic acid and vitamin B complex pills or ampoules. Total serum Hcy level was determined by high-performance liquid chromatography, while serum folic acid and vitamin B(12) were measured by radioimmunoassay. The multivariate analysis showed HD duration (r=0.608; P=0.02) and folic acid serum level (r=-0.580; P=0.03) to be significant predictors of serum tHcy concentration. The multivariate Cox regression analysis of CV mortality revealed diabetes mellitus and heart failure as the most powerful positive predictors, while creatinine, albumin and vitamins intake therapy were negative predictors of CV mortality. Long-term supplementation with the usual doses of vitamins is followed with increased survival in hemodialysis patients. Although total serum Hcy level was not found to be a predictor of overall and CV mortality, the role of hyperHcy. as risk factor for CVD cannot be excluded in hemodialysis patients.

Acute Renal Failure in Transplanted Kidneys.

Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard.

Acute Renal Failure - A Serious Complication in Patients After Kidney Transplantation.

Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails. Along the entire transplantation time course, there is a great demand for novel immune and nonimmune injury biomarkers. The use of these markers can be of great help in the monitoring of kidney injury in potential kidney donors, where acute kidney damage can be overlooked, in predicting acute transplant dysfunction during the early post-transplant periods, or in predicting chronic changes in long term followup. Numerous investigations have demonstrated that biomarkers that have the highest predictive value in acute kidney injury include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that the ideal biomarker to fulfill all the needs in renal transplant has not been identified yet. Although, in many animal models, new biomarkers are emerging for predicting acute and chronic allograft damage, in human allograft analysis they are still not routinely accepted and renal biopsy still remains the gold standard.

The influence of different glucose concentrations in haemodialysis solutions on metabolism and blood pressure stability in diabetic patients.

In recent years the percentage of diabetic patients on haemodialysis has increased. Considering the high frequency of intradialytic hypotensive and hypoglycaemic episodes experienced by these patients, it was the aim of the present study to evaluate the influence of different dialysate glucose concentrations (5.5 mmol/L or 11 mmol/L) on blood pressure and glycaemic regulation, using special dialysis equipment - the GENIUS System. This cross-over, prospective and randomised study, total duration 14 weeks, included 20 diabetic patients on maintenance haemodialysis. Group 1: 9 patients dialysed using dialysate with a glucose concentration of 5.5 mmol/L and after 7 weeks switched to dialysate with a glucose concentration of 11 mmol/L. Group 2: vice versa. Results show a statistically higher number of patients with hypoglycaemic and hypotensive episodes using dialysate with a 5.5 mmol/L glucose concentration. Also, mean serum glucose values were higher during haemodialysis sessions with a glucose dialysate concentration of 11 mmol/L. There were no statistical differences between the groups in laboratory values, HbA1C, insulin doses or in anthropometric parameters. Our results suggest that fewer diabetic patients undergoing haemodialysis using a higher dialysate glucose concentration of 11 mmol/L have hypoglycaemic and hypotensive episodes. Since this dialysate glucose concentration had no influence on lipid or hepatic metabolism, anthropometric parameters and especially HbA/1C values in this short-term study, the long term examination of its effects is warranted.

[Significance of laboratory tests for differential diagnosis of acute renal allograft rejection and acute cyclosporine nephrotoxicity]. / Znacaj laboratorijskih testova za diferencijalnu dijagnostiku akutnog odbacivanja transplantisanog bubrega i akutne ciklosporinske nefrotoksicnosti.

The most frequent causes of renal allograft function deterioration in early postransplantation period are aucte rejection (AR) and acute cyclosporine nephotoxicity (CyA NT). In order to contribute to noninvasive diagnostics in differential diagnosis of these two disorders, glomerular and tubular function in 40 patients during 2-3 weeks after renal transplantation, were followed-up. The results showed that ischaemia, during any act of transplantation provoked functional and structural disorders of renal allografts. During acute rejection serum creatinine level was increased diuresis, sodium and beta-2 microglobulin levels were decreased, whyle there was no significant change in the urinary enzymes ativity. In acute CyA NT there was significantly greater fractional excretion of sodium and beta-2 mikroblobulin, as well as activity of N-acetly-beta-d glukosaminidase and alkaline phosphatase in urine in comparison to other examined groups.

Markers of oxidative stress after renal transplantation.

An increased degree of oxidative stress (OS) in chronic renal failure (CRF) and a possible role of free radicals in CRF have already been described. However, data on OS after renal transplantation are scarce. The aim of the present study was to estimate the degree of OS in renal transplant patients. The study included four groups: 1) 15 haemodialysis patients (HD group), 2) 11 renal transplant patients with stable function (SF group), 3) 12 renal transplant patients with chronic biopsy-proven rejection (CR group), and 4) 10 healthy controls (C group). Markers of OS (malondialdehyde and thiol group levels) and antioxidant activity (glutathione peroxidase and Cu,Zn-superoxide dismutase) were determined in plasma and in red blood cells of all examined individuals. After successful renal transplantation a significant improvement, but not normalization, of antioxidant enzyme activities accompanied by significantly reduced lipid peroxidation were found. In the CR group the degree of OS was increased, and our results suggest that OS may be a relevant pathophysiological factor for CR development.

[Results of kidney transplantation at the Institute of Urology and Nephrology of the Serbian Clinical Center in Belgrade]. / Rezultati transplantacije bubrega u Institutu za urologiju i nefrologiju klinickog centra Srbije u Beogradu. Rezultati Rezultati Rezultati transplantacije bubrega u Institutu za urologiju i nefrologiju Klinickog centra Srbije u Beogradu.

UNLABELLED: Over the period 1980-1992 256 kidney transplantations were carried out in the Institute of Urology and Nephrology, Clinical Centre, Belgrade: 105 (41%) from cadaveric and 151 (59%) from alive related donors. The first kidney transplantation was performed in our Institution in 1974; however, in the first decade only 27 kidney transplantations were performed. Since 1987, thanks to an increasing number of living kidney donors, the number of transplantations continually increased, and after that period an average of 30 kidney transplantations are performed annually (Figure 1). The aim of the study was to establish the survival of patients and grafts, and factors influencing this survival, as well as to determine the causes of patients' death and graft loss. All the patients were followed-up in our outpatient department within at least 5 years to maximum 17 years. Drug combination therapies were changed in the observation period. From 1983 cyclosporin A (CyA) was added to azathioprine (Aza) and prednisolone (Pr). An increasing number of patients with high immunological risks necessitated the strongest initial immunosuppressive treatment with ALG in addition to Aza and Pr. CyA in a dose of 8 mg/kg b.w. was introduced when serum creatinine concentration fell below 300 mumol/L. The triple treatment including CyA, Aza and Pr was the most common maintenance immunosuppressive therapy in our patients. RESULTS: One and five years survived 95% and 75% of patients, and 84% and 52% of grafts. In assessing the impact of donor source, the year of transplantation, and age of donors we obtained the following results: Living related grafts survived better than cadaver grafts, especially during the first posttransplantation year (Figure 2). Furthermore, graft survival rates from 1987 to 1992 were significantly better than those from early period i.e. 1980 to 1986 (Figure 3). The significantly worse survival rate for grafts from donors older than 60 was noted than for grafts from younger donors. Searching for factors influencing the survival, non immunological and immunological differences between donors and recipients were analyzed. Our analysis showed that 50 living related donors were older than 60. In addition, the majority of them were 20 years older than their graft recipients. Two and more HLA mismatches were observed in 46% of our transplant patients, and 20 patients were highly sensitized. However, the immunological risks were higher in living related transplantations: different ABO blood groups, historical positive cross match reaction between donors and recipients (Table 1). A multivariate analysis using Cox proportional hazards model was performed to determine the important independent predictors of graft survival, and it revealed the following factors (Table 2): number of acute rejections, graft function at the end of the first month and until the end of the first posttransplant year, donors' age, and age and sex differences between donors and recipients. The occurrence of acute rejection at any time had a significant negative effect on graft survival. Since better HLA matching is likely to mean less early rejection it could be concluded that HLA matching influenced graft function and survival in our patients. Absence of acute rejection and delayed graft function or acute tubular necrosis were associated with an improvement of the graft function based on serum creatinine concentration, indicating that delayed graft function also influenced graft survival. The relative risk of graft loss was 2 times higher for patients receiving graft from donors older than 60. Until December 1997, when our analysis was done, of 256 kidney transplant patients 156 lost their grafts. The major causes of graft loss (Table 3) in the early period from 1980 to 1986 were non immunological such as acute tubular necrosis, vascular thrombosis and patients death with functioning graft. (ABSTRACT TRUNCATED)