Influence of conversion from calcineurin inhibitors to everolimus on fibrosis, inflammation, tubular damage and vascular function in renal transplant patients.

BACKGROUND: Conversion from calcineurin inhibitor (CNI) to mTOR inhibitors may reduce and even halt the progression of chronic allograft dysfunction (CAD) which is the most important cause of renal allograft loss. We aimed to investigate the effects of conversion from CNI to everolimus on parameters of fibrosis, inflammation, glomerulotubular damage and vascular functions in renal transplant recipients. METHODS: Fifteen stable renal transplant recipients who were under CNI treatment (male/female 13/2, mean age 41 ± 10 years) were enrolled and switched to everolimus. Serum and urinary transforming growth factor-ß (TGF-ß), urinary neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1) were measured as markers of fibrosis, tubular damage and inflammation. As parameters of vascular functions, pulse wave velocity (PWV), augmentation index (AIx), serum asymmetric dimethyl-arginine and fibroblast growth factor-23 (FGF-23) were measured. All these measurements were repeated at the 3rd month of conversion. RESULTS: Estimated GFR (52 ± 7-57 ± 11 ml/min/l.73 m(2), p = 0.02) (was increased after conversion to everolimus. However, serum uric acid levels were significantly decreased (6.21 ± 1.21-5.50 ± 1.39 mg/dL, p = 0.01). Serum TGF-ß levels (8727 ± 2897-1943 ± 365 pg/mL, p = 0.03) and urinary NGAL levels (26 ± 10-12 ± 2 ng/mg creatinine, p = 0.05) were significantly decreased. However, urinary MCP-1, FGF-23, PWV and AIx did not change. Urinary TGF-ß was associated with urinary NGAL (r = 0.62, p = 0.01), urinary MCP-1 (r = 0.68, p = 0.005) and proteinuria (r = 0.50, p = 0.05). CONCLUSION: Conversion from CNI to everolimus resulted in significant decreases of serum TGF-ß and urinary NGAL which may represent less fibrosis and tubular damage. Association of urinary TGF-ß with NGAL and MCP-1 suggests that tubular damage, fibrosis and inflammation may act together for progression of CAD.

Renal Vascular and Ureteral Anatomic Variations in 1859 Potential Living Renal Donors.

BACKGROUND: Renal vascular and ureteral anomalies detected by preoperative computed tomography angiography (CTA) are important for determining the side of the donor nephrectomy and the optimal surgical technique. In the present study, we aimed to examine the renal vascular and ureteral variations in living kidney donor candidates. METHODS: A retrospective analysis was made of 1859 patients who were examined in our clinic as donor nephrectomy candidates between November 2008 and December 2019. Renal CTA images were acquired using a 64-channel multidetector computed tomography scanner, and renal vascular and ureteral variations were evaluated. RESULTS: The prevalence rates of multiple renal arteries on the right and left sides were 18.3% and 22.6%, respectively. The prevalence rates of early branching of the renal arteries, in turn, were 6.3% on the right side and 6.5% on the left side. The overall rate of renal artery variations on both the right and left sides was significantly higher in male individuals than in female individuals (P < .001). Multiple renal veins rates were 28.2% and 2.3% on the right and left sides, respectively, and the short renal veins rates on the right and left sides were 10.1% and 4.35%, respectively. Among the 941 cases undergoing donor nephrectomy, the procedure was completed by laparoscopy in 815 and by conversion from laparoscopic to open surgery in 36. The rate of vascular variations was higher in the conversion to open surgery group than in the laparoscopy group (P = .015). CONCLUSIONS: Careful preoperative assessments of donor renal vascular and ureteral anatomy and variations in CTA are essential for successful and safe renal transplant.

Coronary artery calcification and chronically decreased GFR in living kidney donors.

BACKGROUND: In the presence of decreased glomerular filtration rate (GFR), the risk of morbidity and mortality caused by cardiovascular disease (CVD) is increased markedly. Increased coronary artery calcification (CAC) is proposed as a pathogenetic link between CVD and chronic kidney disease. We examined the frequency and severity of CAC in living kidney donors to test the hypothesis that decreased GFR is associated with increased CAC. METHODS: We used multidetector spiral computed tomography to examine CAC in 101 living kidney donors and 99 age- and sex-matched healthy control subjects without diabetes and a history of coronary artery disease. The extent of calcification was measured by means of the Agatston score. GFR was calculated by using the abbreviated Modification of Diet in Renal Disease formula. The frequency of risk factors for coronary artery disease was compared in kidney donors and controls, and the relation between kidney donors' clinical characteristics and the presence or absence of CAC was examined. RESULTS: CAC frequency and mean calcification scores were similar between kidney donors (13.9%; 4.5 +/- 22.6) and controls (17.2%; 13.2 +/- 89.2). CAC was not associated with decreased GFR, and the correlation between CAC and GFR was not statistically significant. Kidney donors with calcification were more likely to be older (P = 0.003) and male (P = 0.001). Age- and sex-adjusted analysis showed an association between greater parathormone levels (odds ratio, 1.023; 95% confidence interval, 1.001 to 1.045; P = 0.037) and CAC in kidney donors. CONCLUSION: A mild decrease in GFR without the presence of diabetes does not seem to be associated with increased CAC. These findings need to be confirmed in different and larger study populations.

Cardiovascular-renal changes after kidney donation: one-year follow-up study.

BACKGROUND: Long-term consequences of kidney donation are not well known. Most of the studies published were focused on renal risk. In this prospective study, we investigated the changes in cardiovascular function after kidney donation. METHODS: Thirty-eight living kidney donors were included. In addition to 24-hr ambulatory blood pressure monitoring, serum interleukin-6, vascular cell adhesion molecule (VCAM), and asymmetric dimethylarginine levels were measured. Endothelial function was examined by measuring ischemia-induced flow-mediated dilation (FMD) of the brachial artery. All studies were repeated at 3 months and 12 months after kidney donation. RESULTS: The mean serum interleukin-6 levels, both at 3 months and 12 months, were significantly increased as compared to the baseline (P = 0.007 and P < 0.001, respectively). The mean serum asymmetric dimethyl-arginine (P < 0.001) and VCAM levels (P < 0.001) at 12 months were significantly increased as compared to baseline. FMD values at 1 year (9.3% ± 7.1%) were significantly decreased as compared to 3 months (13.0% ± 6.0%, P = 0.001) and baseline (13.9% ± 6.3%, P = 0.002). In multivariate analysis, serum uric acid (P = 0.001), estimated glomerular filtration rate (P = 0.027), and VCAM (P = 0.014) levels were the independent predictors of FMD 12 months after kidney donation. CONCLUSION: Our findings suggest that kidney donation might increase the cardiovascular risk in kidney donors.

Effects of Ganoderma lucidum on obstructive jaundice-induced oxidative stress.

OBJECTIVE: Obstructive jaundice develops after occlusion of the common bile duct. Direct hyperbilirubinaemia, which occurs secondary to the condition, causes various life-threatening pathologies. Cytoprotective effects of Ganoderma lucidum (GL) have previously been shown. In this study, the effects of GL on oxidative stress and oxidant DNA damage in experimental obstructive jaundice were evaluated. METHODS: Sixty Wistar albino adult female rats were randomly divided into six weight-matched equal groups: sham group, bile duct ligated group (BDL); after sham operation 250 mg/kg/d of GL administered group, after sham operation 500 mg/kg/d of GL administered group, after bile duct ligation 250 mg/kg/d of GL administered (GL1BDL) group, and after bile duct ligation 500 mg/kg/d of GL administered (GL2BDL) group. GL polysaccharide was orally administered to the rats via gavage tube once a day for 14 days after bile duct ligation. RESULTS: The plasma malondialdehyde levels of the GL1BDL and GL2BDL groups were significantly lower than those of the BDL group (p < 0.01). The plasma 8-hydroxy-2'-deoxyguanosine levels of the GL1BDL and GL2BDL groups were significantly lower than those of the BDL group (p < 0.001). The liver tissue Cu-Zn superoxide dismutase level of the GL2BDL group was significantly higher than that of the BDL group (p < 0.05). CONCLUSION: GL protected against DNA and liver tissue damage by reducing oxidative stress in obstructive jaundice.

Intracranial calcification and tumoural calcinosis during vitamin D therapy.

Extraskeletal calcifications are frequently observed in patients with chronic renal failure. However, clinically, they usually remain silent. In this report, we describe two patients with massive extraskeletal calcifications that caused significant morbidity. The first patient had tumoural calcification located on the shoulder and the second patient had severe neurological symptoms caused by intracranial calcifications. High calcium phosphorus product and severe secondary hyperparathyroidism were present in both patients. Furthermore, they both received inappropriately high doses of active vitamin D, even though they failed to respond to this therapy. We suggest to monitor closely the calcium, phosphorus and parathyroid hormone levels during calcitriol therapy and to perform parathyroidectomy, without delay, in patients who were resistant to calcitriol.

The effect of renal transplantation on pulmonary function.

In patients with chronic renal failure, mechanical and hemodynamic changes could occur in the lungs without obvious pulmonary symptoms and findings and their effects could pave the way to pulmonary functional disorders. In this study, pulmonary functional disorders and especially alveolocapillary defects, which are frequently seen in uremia, were determined in renal transplanted patients. Pulmonary functions and diffusion capacity were assessed in uremic patients (n = 20) and in successfully transplanted patients (n = 20) without any lung disease or pulmonary edema symptoms and findings. Patients were selected randomly among outpatients who were followed up in a Nephrology and Transplantation Unit. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF25-75) were measured. Single breath carbon monoxide diffusion test and diffusion lung capacity adjusted for hemoglobin concentration (DLAdj) were done. The means of the spirometric values such as FVC, FEV1 and FEV1/FVC were normal in the nondialyzed uremic group, but the PEF25-75 value (68.7%) and diffusion capacity (DLAdj 72.7%) were found to be slightly low. There were 2 patients with normal values and 18 patients with some functional abnormalities in this nondialyzed uremic group. The means of all spirometric parameters and diffusion capacities were found to be normal in the transplanted group. There were 7 patients with normal function and 13 patients with some functional abnormalities in this transplanted group. When the nondialyzed uremic group and the transplanted group were compared statistically, significant differences were found between their spirometric values (except for FVC) and their diffusion capacities. Even though the uremic patients did not show any symptoms, their pulmonary function tests, especially diffusion capacity, were found to be disturbed. Although the transplanted patients as a group had normal mean spirometric values and diffusion capacity there were nevertheless many individual transplanted patients with defective diffusion capacity and abnormal spirometric values.

Diarrhoea following renal transplantation.

In this study, we retrospectively evaluated all attacks of diarrhoea in our renal transplant recipients that came to our medical attention between 1985 and 2000. Also, the clinical features of patients with diarrhoea were compared with the features of recipients without diarrhoea. We diagnosed 41 attacks of diarrhoea in 39 (12.6%) of 308 renal transplant recipients during this time period. An aetiology was detected in 33 (80.5%) of all diarrhoeal episodes and in seven (17.1%) of those the specific agent was diagnosed with the help of stool microscopy. The most frequent causes of diarrhoeal attacks were infectious agents (41.5%) and drugs (34%). Six (14.6%) episodes of diarrhoea were chronic and six were nosocomial. About two-thirds of diarrhoea developed within the late post-transplant period (>6 months). When recipients with diarrhoea were compared with those without diarrhoea, it was seen that diarrhoeal patients had significantly higher creatinine and significantly lower albumin levels when compared with the latter group (p < 0.05). Also, the frequency of antibiotic usage was significantly higher in diarrhoeal patients than in the control group (p < 0.05). Four (10.2%) patients with diarrhoea died despite institution of the appropriate therapy. Two of these deaths were primarily related to diarrhoea and the aetiological agent was Clostridium difficile in both these cases. During the 15-yr study period, 3.6% of all deaths and 5.1% of infection-related deaths in transplant recipients were secondary to diarrhoea. As a result, we observed that infections and drugs were the most frequent causes for diarrhoea in our series of renal transplant recipients. Also, diarrhoea was an important cause of mortality in this patient population.

Cost of renal replacement therapy in Turkey.

BACKGROUND AND RESULTS: By the end 2000, 22224 patients were on renal replacement therapy (RRT) in Turkey. We investigated the cost of RRT in three medical faculties and one private dialysis centre. Yearly expenses were US dollars 22759 for haemodialysis (HD), US dollars 22350 for continuous ambulatory peritoneal dialysis (CAPD), and US dollars 23393 and US dollars 10028, respectively, for the first and second years of transplantation (Tx). In the first year, renal Tx was significantly more expensive than CAPD. However, after the first year of renal transplantation, Tx became significantly more economical than both CAPD and HD. The sum of all yearly RRT expenses for the country was US dollars 488958709, which corresponds to nearly 5.5% of Turkey's total health expenditure. CONCLUSION: Measures such as early construction of vascular access, promoting home dialysis and the reuse of the dialysers, strict control of the use of some expensive drugs like erythropoietin and active vitamin D, and also increasing the number of transplantations, especially if pre-emptive transplantation is possible, should be taken into account in order to reduce these expenses.