Safety and Effectiveness of Marginal Donor in Living Kidney Transplantation.

BACKGROUND: We evaluated the safety and feasibility of living kidney transplantation from marginal donors. PATIENTS AND METHODS: Between June 2006 and March 2015, we performed 61 living related renal transplantations at two renal transplantation centers. Marginal donors were defined as those who were older than 70 years or who had hypertension, reduced renal function, body mass index greater than 30 kg/m(2), or mildly impaired glucose tolerance. We retrospectively compared renal function and graft survival between marginal and standard living donor kidney transplantations. To evaluate renal function, creatinine clearance (CCr) was preoperatively used for donors, and estimated glomerular filtration rate (eGFR) was postoperatively used for donors and recipients. RESULTS: Among 61 donors, 14 (23%) met the marginal criteria, the major reason being hypertension (91%). The mean age tended to be higher in the marginal group. Preoperative eGFR was significantly lower in the marginal group, whereas postoperative renal function decline ratio at two years was not significantly different between the groups (67% vs 67%, P = .960). Five-year graft survival rates were not significantly different between the two groups. However, recipient eGFR 1 year after kidney transplantation was lower in the marginal group than in the standard group (44 ± 8 vs 55 ± 9 in eGFR, P = .003). CONCLUSIONS: No significant differences were observed between the groups regarding donor renal function. Careful marginal donor selection can be safe and feasible for donors and recipients of living kidney transplantation; however, it may have a negative impact on recipient renal function.

Post-transplant renal function and cardiovascular events are closely associated with the aortic calcification index in renal transplant recipients.

INTRODUCTION: The aortic calcification index (ACI) is reported to be closely associated with renal dysfunction and cardiovascular events; however, its implication in renal transplant recipients has not been well examined. In this study, we investigated the relationship between pretransplant ACI, ACI progression, post-transplant renal function, and post-transplant cardiovascular events in renal transplant recipients. PATIENTS AND METHODS: The study from June 1996 to Jan 2012 included 61 renal transplant recipients (living donors, 47; cadaveric donors, 14). The median follow-up period was 60 months. ACI was quantitatively measured on abdominal computed tomography. The relationship between age, dialysis period, estimated glomerular filtration rate (eGFR), and pre- and post-transplant ACI was longitudinally evaluated. Risk factors for post-transplant ACI progression were determined by logistic regression analysis. Patient background and the incidence of post-transplant cardiovascular events were also assessed. RESULTS: The pretransplant ACI (median 4.2%) significantly correlated with age at transplant, dialysis period, and diabetes mellitus. ACI gradually increased up to 2.8 times at 10 years after transplantation. Post-transplant eGFR significantly correlated with ACI progression in patients with chronic kidney disease of stage ≥ 3. Logistic regression analyses showed that age at transplantation, post-transplant period, cadaveric donors, and post-transplant chronic kidney disease stage 3 were risk factors for post-transplant ACI progression. The pretransplant ACI was higher (median 66%) in 3 patients who experienced post-transplant cardiovascular events. CONCLUSIONS: ACI progression closely correlates with age and post-transplant renal function. A high pretransplant ACI is a risk factor for post-transplant cardiovascular events in renal transplant recipients.

A switch from conventional twice-daily tacrolimus to once-daily extended-release tacrolimus in stable kidney transplant recipients.

BACKGROUND: Extended-release tacrolimus (TAC-ER) was developed to provide a more convenient treatment compliance and improve safety by avoiding toxic peak levels. We prospectively evaluated the safety and effectiveness of a 1:1 dose switch from twice-daily tacrolimus to once-daily TAC-ER in stable kidney transplant recipients and assessed their satisfaction with the regimen. PATIENTS AND METHODS: Tacrolimus was switched to TAC-ER (1:1 dose) in 12 kidney transplant recipients with stable renal function from March 2010 to August 2011. The posttransplantation follow-up period was 7.6 ± 4.3 years (range 1.5-13.2 years). No patient had diabetes mellitus in this group. We evaluated the tacrolimus trough levels, serum creatinine, potassium, glucose, glycohemoglobin (HbA1c), and urine protein concentrations once a month from 6 months prior to 1 year after switching. A satisfaction survey for TAC-ER treatment was performed 3 months after the switch. The questionnaire included administration compliance questions such as "forget to take less often," "easy to carry," "easy to store," and "general satisfaction." RESULTS: After the switch to TAC-ER, we observed a quick and sustained 25% decrease in TAC trough levels from 4.8 ± 1.0 to 3.6 ± 0.8 (P = .0002). No significant differences in serum creatinine, potassium, glucose, HbA1c, or urine protein concentration were observed during the 14.6 ± 2.6 months' follow-up period. No recipient experienced acute rejection. The satisfaction survey demonstrated that the stable kidney transplant recipients were satisfied with the switch. CONCLUSIONS: A switch from twice-daily tacrolimus to once-daily TAC-ER (1:1 dose) was safe and effective. TAC-ER can improve treatment compliance in stable kidney transplant recipients.

The usefulness of [131I]-metaiodobenzylguanidine ([131I]-MIBG) scintigraphy performed one week after administration in diagnosing pheochromocytoma.

BACKGROUND: Imaging performed 36-48 h after metaiodobenzylguanidine (MIBG) injection is being widely used in the diagnosis of pheochromocytoma. However, there are some difficult cases to diagnose due to a high concentration of MIBG remaining in the background. We studied the significance of scans on the 7th day after MIBG injection when the concentration of MIBG in the background has declined. METHODS: Imaging was carried out on 11 cases before operation, five cases (eight times) after operation and 12 cases which had been strongly suspected of being pheochromocytoma, but later proved to be non-pheochromocytoma. RESULTS: In all the cases of pheochromocytoma, except one, the tumor imaging was clear 24-72 h after MIBG injection. As for the images after operation and those of the 12 non-pheochromocytoma cases, the scintigram made on the 7th day proved the negative pheochromocytoma. CONCLUSION: This approach was very effective not only for finding early small pheochromocytomas and the remnants of tumors after resection, but also in diagnosing non-pheochromocytoma.

Effect of pressure distribution of shockwave on renal hemorrhage after extracorporeal shockwave lithotripsy: comparison of EDAP LT-01 and Siemens Lithostar.

BACKGROUND: Renal hemorrhage is the most common adverse effect of SWL, and it has been speculated to be related to the type of lithotripter used. METHODS: We investigated the incidence of renal hemorrhage in patients with urinary stones who underwent lithotripsy using either the EDAP LT-01 or the Siemens Lithostar. In addition, we performed in vitro experiments using pressure-sensitive paper in conjunction with gelatin, agar, or porcine tissue models of renal lithotripsy. RESULTS: Thirty-one (16.6%) of 187 kidneys treated with the EDAP LT-01 and 44 (19.6%) of 225 kidneys treated with the Siemens Lithostar showed intrarenal or subcapsular hemorrhage or perinephric hematoma. In particular, the incidence of subcapsular hematoma was significantly higher in the Lithostar-treated patients (P < 0.0001). We discuss our results in light of the patterns of pressure distribution obtained from the two lithotripter units using in vitro models with colorometric, pressure-sensitive paper. CONCLUSION: It appears that the Siemens Lithostar exerts a greater pressure on the renal capsule, which may account for the higher incidence of subcapsular hematoma.

Dynamic SPECT evaluation of renal plasma flow using technetium-99m MAG3 in kidney transplant patients.

OBJECTIVE: The purpose of this study was to evaluate Patlak's graphic analysis method to determine renal plasma flow (RPF) in kidney transplants. METHODS: Dynamic SPECT was performed with 99mTc MAG3 in 12 patients. RPF was determined by both Patlak's graphic analysis method and Russell's method. Ventral, central and dorsal tomographic images of the transplanted kidney were reconstructed to estimate intrarenal distribution of renal plasma flow. RESULTS: The renal influx constant (Ku) calculated by Patlak's graphic analysis method was reproducible and correlated with both serum creatinine (r = -0.88, P < 0.001) and blood urea nitorogen levels (r = -0.82, P < 0.002). However, a significant difference was noted between the RPF values derived from Patlak's graphic analysis method and Russell's method. Ku was corrected by a factor calculated from raw and reconstructed data, and the resulting values were in fair agreement with those determined by Russell's method. CONCLUSION: These methods are useful in evaluating the function of transplanted kidneys.

Effects of endothelin-induced nitric oxide on venous circulation and renal water-electrolyte handling.

To assess the interaction of endothelin (ET) with nitric oxide (NO) and the effects on venous circulation and handling of renal water and electrolytes, ET (1.0 ng/kg/min) or saline was administered with or without three doses (0.27, 2.7 and 27 ng/kg/min for 40 min) of N omega-nitro-L-arginine methyl ester (L-NAME), and NO synthase inhibitor, in anesthetized dogs. ET increased total peripheral resistance (TPR), pulmonary capillary wedge pressure (PCWP), urine flow (UF), and urinary K excretion (UKV), and decreased cardiac output (CO), urinary osmolality (Uosm), renal plasma flow (RPF), and glomerular filtration rate (GFR). L-NAME increased blood pressure (BP), TPR, PCWP, right atrial pressure (RAP), and mean circulatory filling pressure (MCFP), and decreased CO, RPF, and GFR, ET plus L-NAME markedly increased TPR, resistance to venous return, and plasma atrial natriuretic peptide (ANP), but not BP and MCFP, and curtailed the ET-induced responses in UF, UKV, and Uosm. Plasma aldosterone (ALD) was decreased in all groups, but plasma vasopressin (AVP) and renin activity (PRA) were not altered in any group. These results indicate that ET-induced NO formation might mitigate increases in venous as well as arterial vascular resistance and changes in renal handling of water and electrolytes, and might also play an inhibitory role in ANP release but not in PRA or AVP and ALD release.

Impaired vasopressin suppression and enhanced atrial natriuretic hormone release following an acute water load in primary aldosteronism.

The release of arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) and their involvement in renal water and electrolyte metabolism in primary aldosteronism in humans were studied. An oral acute water load (20 ml/kg body weight) was given to each of 12 patients before and after surgical removal of their aldosterone-producing adenoma(s). Plasma AVP and ANH were measured simultaneously, and renal water and electrolyte metabolism and tubular functions were determined. The same water load was given to seven normal subjects and the same parameters were determined. In the presence of mineralocorticoid excess before the operation, plasma AVP was relatively low compared with plasma osmolality (Posm), but was not suppressed in response to decreases in Posm after the water load. Baseline plasma ANH was high and increased further after the water load; urinary dilution and diuresis both remained normal. After the operation, baseline plasma AVP was normal and decreased in response to the decrease in Posm after the water load, with normal urinary dilution and diuresis. Baseline plasma ANH was normal, and did not increase after the water load. The ratio of urinary K and Na clearances and distal tubular reabsorption of Na increased before the operation. These results suggest that there are perturbations of AVP and ANH release in primary aldosteronism, despite the normal urinary dilution after a water load.

Genotype analysis of prepro-vasopressin signal peptide in vasopressin-producing and -non-producing lung tumors.

A polymorphism in the nucleic acid sequence encoding the signal peptide of the human prepro-vasopressin (AVP) has been reported in an AVP producing small cell lung carcinoma (SCLC) cell line. The difference predicts expression in tumor cells of a variant signal peptide with Pro for Leu 11. To clarify whether this difference is required for AVP secretion from SCLC cells and/or reflects increased mutagenesis in malignant tumors, the exon encoding the signal peptide of prepro-AVP in two AVP producing SCLC and 9 non-producing lung tumors was amplified using polymerase chain reaction. The variant sequence was neither found by direct sequencing nor by restriction enzyme analysis. These results suggest that similar to the hypothalamus the normal signal peptide is functional in tumor cells and that the variant signal peptide is not a prerequisite for AVP secretion from SCLC cells.

Cortical laminar necrosis and central pontine myelinolysis in a patient with Sheehan syndrome and severe hyponatremia.

Hypoxic encephalopathy and osmotic demyelination are independent clinical entities. We describe a rare case with these two complications as demonstrated by magnetic resonance imaging (MRI). A 58-year-old woman had adrenal crises twice a decade due to Sheehan syndrome. At the second crisis, hyponatremia was remarkable with consciousness disturbance which was rapidly corrected by intravenous administration of glucocorticoid and hypertonic saline. The maneuver improved consciousness disturbance, but resulted in hypokalemic ventricular fibrillation with circulatory failure. After the normalization of the circulation, however, her consciousness level deteriorated again. Repeated brain MRI revealed acute and chronic phases of cortical laminar necrosis and central pontine myelinolysis.

Central vasopressin blockade enhances its peripheral release in response to peripheral osmotic stimulation in conscious rats.

Increased plasma osmolality results in increased central as well as peripheral release of vasopressin. Experiments were carried out to determine whether, in this circumstance, vasopressin can act centrally to modulate its peripheral release. Prior to the start of a thirty-min i.v. infusion of 2.5 M or 0.15 M NaCl, the rats were given an intracerebroventricular (i.c.v.) injection of a peptide V1/V2 vasopressin antagonist (2 micrograms), OPC-31260 (60 micrograms), a non-peptide V2 antagonist, or 1-desamino-8-D-arginine vasopressin (dDAVP, 5 ng), a V2 agonist. Experiments with the peptide antagonist were carried out in male and non-estrous female rats. Since there were no differences between males and females in the measured responses, experiments with the other two drugs were carried out only in males. Pretreatment with either the V1/V2 antagonist or the V2 antagonist enhanced the increase in plasma vasopressin levels in response to the hypertonic saline infusion by about 50% at the end of 30 min. dDAVP, on the other hand, had no effect. None of the i.c.v. drugs had an affect on either the pressor or bradycardic responses to hypertonic saline infusion. These observations suggest that vasopressin can act centrally in a negative feedback fashion to attenuate its own release into the peripheral circulation in response to increased plasma osmolality.

[Estimation of catecholamine release based on dialyzer clearance rate during hemodialysis].

To estimate catecholamine (CA) release during hemodialysis (HD), plasma-free and conjugated CAs and their dialyzer clearance rates were measured in 10 HD patients (age; 49.8 +/- 15.2 years, duration of HD; 5.8 +/- 5.0 years). Although free dopamine (f-DA) and all conjugated CAs decreased to about one half of the pre-HD levels at the end of HD, no significant change was seen in free norepinephrine (f-NE) and epinephrine (f-E) during HD. For every CA, the clearance rate was the highest in the sulfate and the lowest in the glucuronide form, and NE was the highest in every form. In the comparison between the measured CA and calculated CA using the clearance rate and the pre-HD level, the measured values of f-NE and f-E were significantly higher than the calculated values, unlike the results for f-DA and conjugated CAs. The difference in f-NE between the measured and the calculated values correlated negatively with the change in mean blood pressure (delta MBP), and delta MBP was also correlated with the ultrafiltration volume. From these data, it was suggested that f-NE was released by the decrease of MBP due to the increase of ultra-filtration volume during HD.

Chlorpropamide-induced ADH release, hyponatremia and central pontine myelinolysis in diabetes mellitus.

Chlorpropamide (CPM) has been reported to produce impaired water excretion due to the enhancement of renal vasopressin (ADH) action and/or due to centrally enhanced ADH release, but it is still unknown whether CPM gives rise to ADH release with a subsequent hyponatremia in diabetes mellitus (DM), which, in turn, causes an impairment of the central nervous system. In 3 patients with DM, who developed hyponatremia during the treatment with CPM, an acute water load (WL) was carried out in the presence and absence of the drug, and plasma ADH was determined with plasma and urine osmolalities. Moreover, in 2 cases, MRI scans of the brain were taken. In all the patients, acute WL tests failed to suppress completely ADH release in response to changes in plasma osmolality in the presence of CPM, which, in turn, resulted in the impaired water excretion. In the absence of CPM, an acute WL normally suppressed plasma ADH leading to the diuresis. MRI scans illustrated the presence of central pontine myelinolysis. It is likely that CPM might stimulate ADH release in DM with a subsequent hyponatremia and brain damages.

Changes in plasma vasopressin levels and cardiovascular function due to postural changes in diabetic neuropathy.

Decreases in blood pressure are well known to increase the release of vasopressin. Studies were carried out to investigate whether vasopressin responses to postural changes in blood pressure are maintained in diabetic patients with orthostatic hypotension [DM-OH(+)] as well as non-diabetic patients with orthostatic hypotension [nonDM-OH(+)] and these responses were compared with those observed in normal subjects and diabetic patients without orthostatic hypotension [DM-OH(-)]. After 30 min in the supine position, the upright posture for 40 min was maintained and then the supine for 10 min. Blood pressure and heart rate (HR) were measured every 5 min and plasma vasopressin levels (plasma AVP) were determined every 10 min. In normal subjects and DM-OH(-), mean arterial blood pressure (MABP) did not change, but HR increased significantly by the upright position. Plasma AVP did not change in these groups. On the other hand, in DM-OH(+) MABP fell abruptly and remained to decrease during the upright posture. The HR responses in this group, however, were similar to those in normal control and DM-OH(-). Plasma AVP in DM-OH(+) significantly increased only at 30 min during upright. These increases were significantly greater than those in normal and DM-OH(-). There were significant correlation in changes in MABP (delta MAP) and plasma AVP (delta AVP) in DM-OH(+) (delta AVP = -0.13 MABP + 1.5, r = -0.32, p < 0.01). Relationship between delta MABP and delta AVP in nonDM-OH(+) was similar to that in DM-OH(+). It is concluded that AVP responses to orthostatic hypotension in diabetic and non-diabetic neuropathies were attenuated, but heart rate responses in these patients ware well reserved.

Role of atrial natriuretic peptide in interleukin 1 beta-induced natriuresis in conscious rats.

To assess whether atrial natriuretic peptide (ANP) plays a role in the natriuresis induced by interleukin 1 beta (IL-1 beta), the following experiments were carried out. Experiment (Ex) I: IL-1 beta (7.5 micrograms/kg BW) was given intravenously (i.v.) in conscious hydrated rats (n = 6). Plasma ANP, vasopressin (AVP) osmolality (Posm), Na and K, urine Na (UNa V) and K excretion (UK V), osmolality and flow (UF), and mean arterial blood pressure (MABP) and heart rate were simultaneously determined. In the control group (n = 6), the drug was omitted, and the same protocols were carried out. Ex II: Three mg/kg BW of the specific ANP antagonist, HS-142-1 (HS), was administered i.v. and then, IL-1 beta (7.5 micrograms/kg BW) was given i.v. (n = 6). In the HS alone group (n = 6), IL-1 beta was omitted. The experimental protocols were the same as those in Ex I. IL-1 beta increased significantly plasma ANP and AVP and UNa V, but not UF, accompanied by decreases in Posm and UKV and increases in MABP (ExI). HS inhibited the natriuresis mediated by IL-1 beta, despite increases in plasma ANP and had no influence on plasma AVP and MABP. In the control (ExI) and HS alone (ExII) groups, these parameters did not change, except for decreases in Posm in both groups and increased plasma ANP in the latter. These results suggest that plasma ANP may play an essential role in the IL-1 beta-mediated natriuresis.

Effects of V1- and V2-vasopressin (AVP) antagonists on the pressor, AVP and atrial natriuretic peptide responses to a hypertonic saline infusion in conscious anephric rats.

To examine the role of vasopressin (AVP) receptors in the regulation of the hemodynamics and release of atrial natriuretic peptide (ANP), and the participation of renal nerve inputs in the osmotic AVP release, hypertonic saline (HS) was infused into conscious, bilaterally nephrectomized rats with non-peptide, selective antagonists for the V1-receptor or V2-receptor of AVP. In the control group, HS alone increased mean arterial pressure, plasma ANP and AVP, plasma volume and plasma osmolality, and decreased the heart rate. In the V1-receptor antagonist group, an increase in the mean arterial pressure and a decrease in heart rate were completely abolished and an increase in plasma ANP was attenuated. In the V2-receptor antagonist group, increases in mean arterial pressure and plasma ANP and a decrease in heart rate were attenuated. However, the ratio of the changes in heart rate to the changes in mean arterial pressure in the V2-receptor antagonist group is significantly higher than that in the control group. In both experimental groups, increases in plasma AVP, plasma volume and plasma osmolality were not different from those in the control group. These results suggest that a HS-induced increase in mean arterial pressure is mediated by the pressor effect of AVP, mainly through V1-receptors, and that the depressor effect of AVP through V2-receptors may not influence tonically HS-induced hypertension. Moreover, HS-induced increase in plasma ANP is mediated mainly by increases in plasma volume and blood pressure, but may not be affected by a direct action of AVP to the heart. Renal afferent nerve inputs may not have effects on the regulation of osmotic AVP release.