Effect of losartan on the recoverability of renal function in anuric and oliguric patients with a solitary obstructed kidney: a double-blind randomized placebo-controlled trial.

OBJECTIVES: To assess the role of the angiotensin receptor blocker losartan on the recoverability of renal function after de-obstruction in patients with anuria and oliguria. MATERIALS AND METHODS: This was a double-blind randomized placebo-controlled trial in anuric or oliguric patients with calcular obstruction of solitary kidney. Patients with an anomalous kidney or those with an American Society of Anesthesiology score of >3 were excluded. After relief of obstruction, patients were allocated to receive either losartan potassium 25 mg or placebo for 3 months. Serum creatinine (sCr) and renographic glomerular filtration rate (GFR) were measured at nadir and after 3 months. Changes in sCr and renographic GFR were calculated by subtracting the values at nadir from those at 3 months. Improvement, stabilization or deterioration of sCr and renographic GFR were defined as percentage increase or decrease from nadir ≥10%, while changes <10% were considered as stabilization. RESULTS: A total of 76 patients completed 3 months of follow-up. Demographics and peri-operative data were comparable in the two groups. The median (range) sCr change was -1.05 (-1.8, 0.4) and -0.5 (-1.3, 0.1) mg/dL in the losartan and placebo, groups, respectively (P = 0.07). In the losartan group, renographic GFR had improved in 26 (59.1%) and deteriorated in six (13.6%) patients, while, in the placebo group, it had improved in eight (25%) and deteriorated in 10 patients (31.3%; P = 0.01). Losartan also enhanced renographic GFR improvement vs placebo by a median (range) of 6.9 (-9, 44) vs 1.4 (-10, 32) mL/min (P = 0.004). CONCLUSIONS: In patients with anuria and oliguria, losartan treatment contributes to renal function recoverability after relief of calcular obstruction of the solitary kidney.

Pericardectomy after pericarditis constrictiva led to onset of transplant kidney function after 98 days of anuric kidney graft: a case report.

BACKGROUND: Constrictive pericarditis is easily overlooked and can lead to severe problems in hemodynamics and end-organ perfusion, in our patient leading to 98 days of anuria after living kidney transplantation. This was completely reversible after pericardectomy. CASE PRESENTATION: A 43-year-old female caucasian patient received a living kidney donation from her mother. She had developed end-stage renal disease 2 years prior due to nephrotic syndrome linked to graft-versus-host disease after allogenic stem-cell transplantation for aplastic anemia. The graft showed insufficient function already in the early postoperative phase. Dialysis was paused after surgery, but the patient developed hypervolemia with ascites and edema in the lower extremities. Doppler ultrasonography showed scarce perfusion, with intrarenal arterial waveforms without end-diastolic flow. The venous perfusion profiles showed pulsatile retrograde flow. There was no identifiable reason for a primary vascular perfusion problem on ultrasonography or transplant kidney angiography. Kidney transplant biopsy revealed no rejection but extensive acute tubular necrosis. Three weeks after transplantation, the patient developed an acute anuric graft failure caused by severe cardiac decompensation. Echocardiography revealed a previously unnoticed constrictive pericarditis, which could be confirmed in a cardio computed tomography scan. The constrictive pericarditis had not been apparent on previous x-rays, computed tomography scans, or echocardiographies, including those for transplantation evaluation. Conservative management of the constrictive pericarditis was not successful and the graft remained anuric. Eventually, the patient underwent pericardectomy 16 weeks after kidney transplantation. Shortly after surgery, the graft started urine production again, which significantly increased within a few days. The clearance improved and 2 weeks later, the patient was free from dialysis. CONCLUSIONS: This case illustrates that special attention should be given to the pericardium during transplant evaluation, especially for patients who previously underwent stem-cell transplantations, chemotherapy or radiation.

Renin-angiotensin system blockers and residual kidney function loss in patients initiating peritoneal dialysis: an observational cohort study.

BACKGROUND: Although angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) have been shown to preserve residual kidney function in a select group of Asian patients undergoing continuous ambulatory peritoneal dialysis (PD) in two small randomized clinical trials, the effectiveness of these drugs has yet to be demonstrated in a more diverse population of patients with multiple comorbid conditions. We investigated the association between ACEI/ARB use and development of recorded anuria in a cohort of patients initiating PD in the U.S. METHODS: We conducted a retrospective observational cohort study using the US Renal Data System and electronic health records data from a large national dialysis provider. We identified adult patients who initiated PD from 2007 to 2011. Only patients who participated in the federal prescription drug benefit program, Medicare Part D, for the first 90 days of dialysis were included. Patients who filled a prescription for an ACEI or ARB during those 90 days were considered users. We applied Cox proportional hazards models to an inverse probability of treatment-weighted (IPTW) cohort to estimate the hazard ratio (HR) for anuria (24-h urine volume < 200 ml) in ACEI/ARB users vs. non-users. RESULTS: Among 886 patients, 389 (44%) used an ACEI/ARB. Almost a third of these patients were black or Hispanic, and more than a quarter had comorbidities that would have excluded them from the randomized clinical trials of ACEI/ARB. Two hundred eighty patients reached anuria over 840 person-years of follow-up, for a composite event rate of 33 events per 100 person-years. We found no clear association between ACEI/ARB use and progression to anuria [HR: 0.86, 95% CI: 0.73-1.02]. CONCLUSIONS: ACEI/ARB use is common in patients initiating PD in the U.S. but was not associated with a lower risk of anuria. Residual confounding by unmeasured variables is an important limitation of this observational study. Still, these findings suggest that pragmatic clinical trials are warranted to test the effectiveness of ACEI/ARB in slowing the decline of residual kidney function in a diverse population of peritoneal dialysis patients with multiple comorbid conditions.

Subcapsular Hematoma Causing Anuria After Renal Graft Trauma.

A 67-year-old man presented to the emergency department 22 hours after a trauma to his kidney graft. He was asymptomatic during the first 10 hours, then he became anuric. His serum creatinine level was 2.73 mg/dL (baseline, 0.7 mg/dL), and his hemoglobin concentration was 13.1 g/dL. Computer tomography showed a 4-cm subcapsular hematoma without active bleeding. He underwent urgent decompression of the hematoma, and we did not find any active bleeding or parenchymal laceration. Urinary output had already recovered by the end of surgery without early or late complications. In conclusion, subcapsular hematoma, complicating a traumatic event on a kidney graft, can lead to a progressive parenchymal compression resulting in anuria. So, although in the absence of anemia, such events require urgent surgical decompression. Symptoms cannot be immediate, so all the graft trauma should be investigated with early ultrasound. Little is known in the case of major renal trauma but mildly symptomatic. Probably surgical exploration is better than observation to prevent possible early and late complications such as organ rejection or a Page kidney.

Three Versus 4 Daily Exchanges and Residual Kidney Function Decline in Incident CAPD Patients: A Randomized Controlled Trial.

BACKGROUND: Incident patients treated with continuous ambulatory peritoneal dialysis (CAPD) are often prescribed either 3 or 4 exchanges per day. However, the effects on residual kidney function and clinical outcomes of 3 versus 4 exchanges are not known. STUDY DESIGN: Prospective, randomized, controlled, open-label study. SETTING & PARTICIPANTS: Incident CAPD patients aged 18 to 80 years with glomerular filtration rates (GFRs; mean of renal urea and creatinine clearance from a 24-hour urine collection) ≥ 2mL/min and urine volume ≥ 500mL/d. Exclusion criteria included refusal for informed consent, history of maintenance hemodialysis therapy or transplantation, or limited life expectancy. INTERVENTION: 24-month intervention with 3- or 4-exchange CAPD using glucose-based peritoneal dialysis fluids. OUTCOMES: Primary outcomes were GFR, urine volume, and anuria-free survival. Secondary outcomes included peritonitis, patient survival, and technique survival. RESULTS: The study recruited 139 patients, 70 in the 3-exchange group and 69 in the 4-exchange group. Baseline body mass indexes were 21.4±3.0 and 21.9±3.2kg/m2 for the 3- and 4-exchange groups, respectively (P=0.4). After 24 months, for 3 versus 4 exchanges, GFR (1.6±2.0 vs 1.7±1.9mL/min; P=0.8), urine volume (505±522 vs 474±442mL/d; P=0.8), and anuria-free survival (log-rank test statistic = 0.055; P=0.8) did not differ between groups, but Kt/V (1.95±0.39 vs 2.19±0.48; P=0.03) and ultrafiltration (404±499 vs 742±512mL/d; P=0.004) were lower in the 3-exchange group. The 3-exchange group had nominally longer peritonitis-free survival time (log-rank test statistic = 3.811; P=0.05), and nominally fewer patients had peritonitis in this group, though this was not statistically significant (13% vs 26%; P=0.06). Patient survival (log-rank test statistic = 0.978; P=0.3) and technique survival (log-rank test statistic = 0.347; P=0.6) were similar between groups. LIMITATIONS: Single-center design; no formal sample-size calculations. CONCLUSIONS: In this small trial, CAPD regimens with 3 and 4 exchanges had similar effects on residual GFR, urine volume, and time to anuria. Incremental peritoneal dialysis starts appear safe when patients are monitored.

Predictive value of the RIFLE urine output criteria on contrast-induced nephropathy in critically ill patients.

BACKGROUND: To investigate the predictive value of decreased urine output based on the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage renal disease (RIFLE) classification on contrast- induced acute kidney injury (CA-AKI) in intensive care (ICU) patients. METHODS: All patients who received contrast media (CM) injection for CT scan or coronary angiography during a 3-year period in a 24 bed medico-surgical ICU were reviewed. RESULTS: Daily serum creatinine concentrations and diuresis were measured for 3 days after CM injection. We identified 23 cases of CA-AKI in the 149 patients included (15.4 %). Patients who developed CA-AKI were more likely to require renal replacement therapy and had higher ICU mortality rates. At least one RIFLE urine output criteria was observed in 45 patients (30.2 %) and 14 of these 45 patients (31.1 %) developed CA-AKI based on creatinine concentrations. In 30 % of these cases, urine output decreased or didn't change after the increase in creatinine concentrations. The RIFLE urine output criteria had low sensitivity (39.1 %) and specificity (67.9 %) for prediction of CA-AKI, a low positive predictive value of 50 % and a negative predictive value of 87.2 %. The maximal dose of vasopressors before CM was the only independent predictive factor for CA-AKI. CONCLUSIONS: CA-AKI is a frequent pathology observed in ICU patients and is associated with increased need for renal replacement therapy and increased mortality. The predictive value of RIFLE urine output criteria for the development of CA-AKI based on creatinine concentrations was low, which limits its use for assessing the effects of therapeutic interventions on the development and progression of AKI.

Duration of anuria predicts recovery of renal function after acute kidney injury requiring continuous renal replacement therapy.

BACKGROUND/AIMS: Little is known regarding the incidence rate of and factors associated with developing chronic kidney disease after continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients. We investigated renal outcomes and the factors associated with incomplete renal recovery in AKI patients who received CRRT. METHODS: Between January 2011 and November 2013, 408 patients received CRRT in our intensive care unit. Of them, patients who had normal renal function before AKI and were discharged without maintenance renal replacement therapy (RRT) were included in this study. We examined the incidence of incomplete renal recovery with an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) and factors that increased the risk of incomplete renal recovery after AKI. RESULTS: In total, 56 AKI patients were discharged without further RRT and were followed for a mean of 8 months. Incomplete recovery of renal function was observed in 20 of the patients (35.7%). Multivariate analysis revealed old age and long duration of anuria as independent risk factors for incomplete renal recovery (odds ratio [OR], 1.231; 95% confidence interval [CI], 1.041 to 1.457; p = 0.015 and OR, 1.064; 95% CI, 1.001 to 1.131; p = 0.047, respectively). In a receiver operating characteristic curve analysis, a cut-off anuria duration of 24 hours could predict incomplete renal recovery after AKI with a sensitivity of 85.0% and a specificity of 66.7%. CONCLUSIONS: The renal outcome of severe AKI requiring CRRT was poor even in patients without further RRT. Long-term monitoring of renal function is needed, especially in severe AKI patients who are old and have a long duration of anuria.

The importance of overhydration in determining peritoneal dialysis technique failure and patient survival in anuric patients.

PURPOSE: Loss of residual renal function (RRF) is associated with an increased risk for peritoneal dialysis (PD) technique failure and patient death. We wished to determine which factors were associated with PD technique failure and patient mortality once urine output had fallen to <100 mL/day. METHODS: We followed 183 PD patients who lost RRF and who had measurements taken at that time of PD small solute clearances, ultrafiltration volume, PD transport status and multiple frequency bioelectrical impedance assessments (MFBIA) of extracellular water (ECW). RESULTS: 119 (65%) patients had PD technique failure or died during a median follow-up of 20.8 (10.5-36) months. This group had more men (58.8% vs. 31.9%, p = 0.011), and were older 57.9 ± 14.7 vs. 49.3 years (p = 0.002). These patients had a higher median C-reactive protein 5.5 [4.8-8.2] vs (5.0 [2-6] p = 0.013), and greater comorbidity (Davies grade 1 [0-1] vs. 0[0-1], p<0.001, and a higher ratio of ECW/TBW (0.45 ± 0.07 vs 0.42 ± 0.04, p<0.001). There were no differences in icodextrin usage, small solute clearance or ultrafiltration volumes. On multivariate Cox regression, ECW excess was significantly associated with PD technique failure and patient survival (ß 1.09, p<0.001 and ß1.17, p = 0.005), respectively. CONCLUSIONS: Loss of urine output requires PD to provide both adequate solute clearances and volume control. We found that PD technique failure and patient death were associated with ECW excess. Prospective interventional studies are required to determine whether correction of volume status improves PD patient outcomes.

Focal segmental glomerular sclerosis recurrence with massive proteinuria and anuria immediately after kidney transplantation.

Here, we report a case of focal segmental glomerular sclerosis (FSGS) recurrence immediately (47 minutes) after transplantation. A 1-hour biopsy specimen showed large periodic acid-Schiff-positive granules within the cells of the swollen proximal tubule, while electron microscopy revealed podocyte swelling and partial foot process effacement. These findings were worse on day 2 biopsy. Massive proteinuria and anuria were then observed. Two courses (2 × 2 times) of plasmapheresis and rituximab were administered, and the graft function gradually recovered. A day 22 biopsy specimen showed improvement in findings compared to those observed on day 2. One year after transplantation, no signs of FSGS recurrence are evident, and graft function remains good.

The interdialytic weight gain: a simple marker of left ventricular hypertrophy in children on chronic haemodialysis.

Despite multiple advances in haemodialysis (HD) technology over the years, the morbidity and mortality of HD patients remain unacceptably high. Cardiovascular disease is the most common cause of death, and left ventricular hypertrophy (LVH), seen in two-thirds of children on dialysis, is a significant contributor. The importance of volume control is increasingly recognized by nephrologists and now considered to be as important as urea kinetics, both in the day-to-day management and the long-term outcome of dialysis patients. The results published by Paglialonga et al. ( 10.1007/s00467-014-3005-2 ) in this issue of Pediatric Nephrology clearly demonstrate that there is a significant correlation between interdialytic weight gain (IDWG) and LVH in oligoanuric children on chronic HD and that children with an IDWG of >4 % are at high risk of LVH. One common practice to achieve euvolaemia is to prescribe very high ultrafiltration rates. However, both volume overload and aggressive fluid removal can induce circulatory stress and multi-organ injury. In adults, ultrafiltration rates of >1.24 % body weight per hour, even if well tolerated, are associated with a significant increase in mortality. Nephrologists should be aware of the risk of a high ultrafiltration rate, especially if tolerance is obtained by a positive dialysate-to-plasma sodium gradient. Haemodiafiltration, which allows for higher ultrafiltration rates with greater intradialytic haemodynamic stability, or more frequent and longer dialysis sessions allow for safe and effective fluid removal.

Does the inhibition of renin-angiotensin system decrease inter-dialytic weight gain in anuric hemodialysis patients?

OBJECTIVE: Knowledge about the inhibition of centrally located angiotensin-I (AT-I) receptors by highly lipophilic AT-I receptor blockers and its' effect are limited with experimental studies. Thus, we aimed to investigate the effect of Telmisartan on Inter-dialytic weight gain (IDWG) % and echocardiographic measurements in anuric hemodialysis (HD) patients. PATIENTS AND METHODS: A total of forty-one anuric HD patients with ≥ 6 months maintenance on HD were included in this prospective, randomized and self-controlled study. Four weeks prior the study, angiotensin converting enzyme blockers and AT-I receptor blocker drugs were stopped. Patients were assessed three times during the study protocol. These are baseline, three months later (without Telmisartan period) and three months after Telmisartan therapy. RESULTS: IDWG % was significantly decreased in the period of with Telmisartan compared to period without Telmisartan (5.6 ± 1.0% vs 5.3 ± 1.0%, p = 0.03). After the administration of Telmisartan left ventricule end-diastolic diameter (LVEDD) (p = 0.001) and inferior vena cava diameter (IVCD) (19.1 ± 3.8 mm vs 17.3 ± 4.2 mm, p = 0.001) were significantly decreased compared to the period of without Telmisartan. Despite of significantly changes observed in IVCD and LVEDD measurements in a period without Telmisartan, there was no significantly difference in left ventricular mass index (LVMI) measurements in this period. However, LVMI was significantly regressed after the administration of Telmisartan (269.3 ± 82.7 g vs 256.3 ± 70.3 g, p = 0.003 respectively). CONCLUSIONS: Treatment of anuric HD patients with Telmisartan at a dose of 40 mg a day reduces IDWG%, LVEDD and IVCD measurements. Further studies investigating the long-term effect of these beneficial effects on clinical outcomes are necessary.

Interdialytic weight gain in oligoanuric children and adolescents on chronic hemodialysis.

BACKGROUND: Little is known about the clinical impact of interdialytic weight gain (IDWG) on oligoanuric children undergoing chronic hemodialysis (HD). METHODS: We retrospectively assessed IDWG, left ventricular mass index (LVMI) and its changes (ΔLVMI), pre-HD systolic and diastolic blood pressure (DBP), residual urine output, Kt/V, the frequency of intradialytic symptoms, normalized protein catabolic rate, and the 3-month change in the dry weight of 16 hemodialyzed oligoanuric patients with a median age of 14.8 years (range 5.0-17.9). RESULTS: There was a significant correlation between IDWG and median LVMI (r 0.55, p = 0.026), which was 27.3 g/m(2.7) (22.5-37.6) in the patients with a median IDWG of <4 %, and 44.3 g/m(2.7) (28.2-68.7) in those with a median IDWG of >4 % (p = 0.003). None of the four patients with an IDWG of <4 % showed left ventricular hypertrophy, compared with 10 of the 12 patients (83.3 %) with an IDWG of >4 % (p = 0.003); the former also had a better median ΔLVMI (-33.5 % vs -13.0 %; p = 0.02) and a lower median DBP sds (0.24 vs 1.72, p = 0.04). CONCLUSIONS: There is a significant correlation between IDWG and LVMI in pediatric oligoanuric patients on chronic HD: those with an IDWG of >4 % are at a higher risk of left ventricular hypertrophy.

Effect of gradually lowering dialysate sodium concentration on the interdialytic weight gain, blood pressure, and extracellular water in anuric hemodialysis patients.

BACKGROUND: The majority of hemodialysis (HD) patients are overhydrated and have high interdialytic weight gain (IDWG) which induces increased blood pressure (BP). The positive sodium balance resulting from a high sodium diet, a high dialysate sodium concentration (DNa), or a combination of both is major causes of this disease. We evaluated the effects of lowering DNa on IDWG, BP, and volume status in anuric HD patients with dietary sodium restriction. METHODS: Thirty-two patients were enrolled in this study and the period was divided by phase 1 and 2 according to DNa which decreased from 140 to 135 mEq/L at a rate of 1 mEq/L per month; phase 1, 140 mEq/L; phase 2, 135 mEq/L. We compared the IDWG, BP, volume status measured by multifrequency bioimpedance spectroscopy, and adverse events such as intradialytic hypotension, cramps, and headache of both phases. RESULTS: The IDWG was significantly reduced by 0.39 ± 0.38 kg (p = 0.000). Pre-dialysis BP showed significant reduction (systolic pressure 146 ± 18 vs. 138 ± 22 mmHg; p = 0.012, diastolic pressure 80 ± 10 vs. 75 ± 11 mmHg; p = 0.008). Pre-dialysis extracellular water (ECW) was reduced significantly by 0.13 ± 2.22 L (p = 0.02). There was no significant increase in adverse events (all p > 0.05). CONCLUSIONS: This study showed that gradually lowering DNa could bring a significant reduction in pre-dialysis IDWG, BP, and ECW without increased adverse events. Large and crossover designed study will be needed to demonstrate the clear causal relationship.

Reduction of cystometric bladder capacity and bladder compliance with time in patients with end-stage renal disease.

BACKGROUND/PURPOSE: Reduced bladder capacity and compliance in patients with end-stage renal disease (ESRD) may affect storage and voiding function after kidney transplantation. This study evaluated the bladder capacity, compliance, and lower urinary tract dysfunction in ESRD patients with duration after dialysis and anuria. MATERIALS AND METHODS: Adults with ESRD on kidney transplantation waiting list were consecutively enrolled. The survey items included videourodynamic study (VUDS), renal ultrasound, and cystoscopy. The analytical variables assessed included the duration of dialysis, the duration of anuria, cystometric bladder capacity and bladder compliance, voiding phases in VUDS, and cystoscopic findings. RESULTS: A total of 62 patients with a mean dialysis duration of 58.9 ± 6.3 months were enrolled. The mean cystometric bladder capacity was 178 ± 14 mL and decreased significantly with duration of dialysis (p < 0.001). Anuria was diagnosed in 26 patients, and the mean cystometric bladder capacity decreased significantly with the duration of anuria (p = 0.002). Among the 26 patients with anuria, 16 had a poor bladder compliance. VUDS revealed abnormal storage function in 44 (71.0%) patients and bladder outlet obstruction due to bladder neck dysfunction or urethral narrowing in the voiding phase in 32 (51.6%). Abnormal cystoscopic findings were also noted in 30 (48.4%) patients. CONCLUSION: Cystometric bladder capacity and bladder compliance decreased with longer duration of dialysis, and the presence of anuria contributed to further decreases in cystometric bladder capacity and bladder compliance. More than two-thirds of patients with ESRD had abnormal findings on VUDS.

Effects of different dialysate calcium concentrations on intradialysis hemodynamic stability.

BACKGROUND: The interplay of correct solute mass balances, such as those of sodium (Na+), potassium (K+) and total calcium (tCa) (Na+MB, K+MB and tCaMB, respectively) with adequate ultrafiltration volumes (VUF) is crucial to achieving hemodynamic stability during hemodialysis (HD). METHODS: Twenty-two stable anuric uremic patients underwent three 4-hour bicarbonate HD sessions, each with a different dialysate tCa concentration (1.25, 1.375 and 1.50 mmol/L). The GENIUS dialysis system (Fresenius Medical Care, Germany) was used. Volumes of blood and dialysate processed, VUF and dialysate Na+ and K+ concentrations were prescribed to be the same. Hourly measurements of plasma water ionized Ca (Ca++), Na+ and K+ were made, and their trends analyzed. tCaMBs, Na+MBs and K+MBs were determined. Systolic (SBP), diastolic (DBP) blood pressure, mean arterial pressure (MAP) and heart rate (HR) trends during dialysis were analyzed. RESULTS: Mean hourly plasma water Ca++ concentrations were statistically significantly higher with a dialysate tCa concentration of 1.50 mmol/L. Mean tCaMBs were positive (diffusion gradient from the dialysate to the patient), increasing with increasing dialysate tCa concentrations (+75 ± 122 mg, +182 ± 125 mg, +293 ± 228 mg, respectively). Their difference was statistically significant (p<0.0005). Mean Na+MBs and K+MBs were not statistically significantly different. SBP, DBP, MAP and HR were not statistically significantly different among the 3 treatments. CONCLUSIONS: These highly controlled experiments showed that hemodynamic stability does not appear to be statistically significantly influenced by any specific dialysate tCa concentration in this peculiar subset of patients.

Investigating the mechanism for maintaining eucalcemia despite immobility and anuria in the hibernating American black bear (Ursus americanus).

Ursine hibernation uniquely combines prolonged skeletal unloading, anuria, pregnancy, lactation, protein recycling, and lipolysis. This study presents a radiographic and biochemical picture of bone metabolism in free-ranging, female American black bears (Ursus americanus) that were active (spring bears and autumn bears) or hibernating (hibernating bears). Hibernating bears included lactating and non-lactating individuals. We measured serum calcium, albumin, inorganic phosphate, creatinine, bone specific alkaline phosphatase (BSALP), CTX, parathyroid hormone, insulin-like growth factor-I (IGF-l), leptin, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and sclerostin from 35 to 50 tranquilized hibernating bears and 14 to 35 tranquilized spring bears. We compared metacarpal cortical indices (MCI), measured by digital X-ray radiogrammetry, from 60 hunter-killed autumn bears and 79 tranquilized, hibernating bears. MCI was greater in autumn than winter in younger bears, but showed no seasonal difference in older bears. During hibernation eucalcemia was maintained, BSALP was suppressed, and CTX was in the range expected for anuria. During hibernation 1,25(OH)(2)D was produced despite anuria. 1,25(OH)(2)D and IGF-I were less in hibernating than spring bears. In a quarter of hibernating bears, sclerostin was elevated. Leptin was greater in hibernating than spring bears. In hibernating bears, leptin correlated positively with BSALP in non-lactating bears and with CTX in lactating bears. Taken together the biochemical and radiographic findings indicate that during hibernation, bone turnover was persistent, balanced, and suppressed; bone resorption was lower than expected for an unloaded skeleton; and there was no unloading-induced bone loss. The skeleton appears to perceive that it was loaded when it was actually unloaded during hibernation. However, at the level of sclerostin, the skeleton recognized that it was unloaded. During hibernation leptin appeared anabolic in non-lactating bears and catabolic in lactating bears. We hypothesize that ursine hibernation may represent a natural model in which suppression of the sympathetic nervous system prevents unloading-induced bone loss by influencing leptin's skeletal effects and preventing transmission of loading information.

Variability of pulse wave velocity and mortality in chronic hemodialysis patients.

We have already demonstrated that in chronic hemodialysis (HD) patients, the cyclic variations in both hydration status and blood pressure are responsible for changes in pulse wave velocity (PWV). The aim of this study is to verify whether the cyclic variation of PWV influences mortality in dialysis patients. We studied 167 oligoanuric (urinary output <500 mL/day) patients on chronic standard bicarbonate HD for at least 6 months. They performed 3 HD sessions of 4 hours per week. Patients were classified into 3 groups: normal PWV before and after dialysis (LL); high PWV before and normal PWV after dialysis (HL); and high PWV before and after dialysis (HH). The carotid-femoral PWV was measured with an automated system using the foot-to-foot method. Analysis of variance was used to compare the different groups. The outcome event studied was all-cause mortality and cardiovascular mortality. The PWV values observed were LL in 44 patients (26.3%); HL in 53 patients (31.8%); and HH in 70 patients (41.9%). The 3 groups of patients are homogenous for sex, age, and blood pressure. The HH group had a higher prevalence of (P<0.001) ASCVD. It is interesting that the distribution of patients in the 3 groups is correlated with the basal value of PWV. In fact, when the basal measure of PWV is elevated, there is a higher probability that an HD session cannot reduce PWV (<12 ms). A total of 53 patients (31.7%) died during the follow-up of 2 years: 5 patients in the LL group (11.4%); 16 in the HL group (30.2%); and 32 in the HH group (50.7%) (LL vs. HL, P=0.047; LL vs. HH, P<0.00001; HL vs. HH, P=0.034). We evidence for the first time that different behaviors of PWV in dialysis subjects determine differences in mortality.