Calcific uremic arteriolopathy (CUA) is a rare, life-threatening disease, typically affecting patients with end-stage renal disease. It is characterized by widespread vascular calcification, endothelial fibrosis and end-organ ischemia. The mortality rate is high with infection and sepsis being the most common causes of death. Common therapies include restoration of calcium and phosphorous homeostasis, wound care and pain control. Although soft tissue calcification is a known complication in children with advanced renal disease, the incidence of CUA in pediatrics remains unknown. Additionally, current literature regarding its management in pediatric patients is lacking. We report the case of a 17-year-old African–American male patient with end-stage renal disease secondary to Wegener’s granulomatosis who developed CUA after 3 years on peritoneal dialysis. Treatment with sodium thiosulfate (STS) and hyperbaric oxygen (HBO) therapy alone was ineffective, forcing the patient to undergo bilateral below the-knee-amputation (BKA) 5 months after presentation. It was not until peritoneal dialysis had been changed to daily hemodialysis, while continuing STS and HBO therapy, that the patient demonstrated complete resolution of CUA on repeat bone scan. Based on these findings, and the extremely high mortality rate associated with this disease, CUA management requires early and aggressive intervention with multi-faceted therapy, including prompt conversion from peritoneal dialysis to hemodialysis, STS infusions and hyperbaric oxygen therapy.

Background

Several studies have shown an association between erythropoietin-stimulating agent (ESA) responsiveness and mortality in chronic kidney disease (CKD) patients. In our present study, we examined the association between prescribed ESA dose and mortality in peritoneal dialysis (PD) and hemodialysis (HD) patients. We hypothesized that PD patients received lower ESA dose for the same achieved hemoglobin compared to HD patients and that ESA dose-mortality associations were different between PD and HD patients.

Methods

We compared the prescribed doses of ESA between 139,103 HD and 10,527 PD patients treated in DaVita dialysis clinics from 7/2001 through 6/2006 using adjusted Poisson regression and examined mortality-predictability of prescribed ESA dose and ESA responsiveness index (ESA/hemoglobin) in PD and HD with follow-up through 6/2007 using Cox regression models.

Results

Poisson adjusted ratio of ESA dose of HD to PD was 3.6 (95% CI 3.5-3.7). In PD patients, adjusted all-cause death hazard ratios (HR) for ESA doses of 3,000-5,999, 6,000-8,999 and ≥9,000 U/week (reference <3,000 U/week) were 0.97 (0.87-1.07), 0.85 (0.76-0.95) and 1.08 (0.98-1.18), respectively; whereas in HD patients across commensurate ESA dose increments of 10,000-19,999, 20,000-29,999 and ≥30,000 U/week (reference <10,000 U/week) were 1.14 (1.11-1.17), 1.54 (1.50-1.58) and 2.15 (2.10-2.21), respectively. In PD and HD patients, the adjusted death HR of the 4th to 1st quartile of ESA responsiveness index were 1.14 (1.04-1.26) and 2.37 (2.31-2.43), respectively.

Conclusions

Between 2001 and 2006, most PD patients received substantially lower ESA dose for same achieved hemoglobin levels, and low ESA responsiveness was associated with higher mortality in both HD and PD patients.

Outcomes for pediatric SBT patients requiring perioperative RRT in the PICU remain unknown. The objectives were to document our center's experience with PICU SBT patients receiving perioperative RRT and to identify variables predictive of survival to discharge. A retrospective chart review of patients (ages, 0-18 yr) between January 1, 2000 and December 31, 2011 that received RRT within a SBT perioperative period and were transplanted at our university-affiliated, tertiary care children's hospital was performed. Six SBT patients received perioperative RRT (ages, 5-12 yr). Three patients (50%) survived to hospital discharge. Among survivors, RRT was required for a total of 1-112 days (mean, 49.7 days). All three survivors survived to hospital discharge without renal transplantation and free of RRT. There was a trend toward increased survival among older patients receiving RRT (p = 0.05). Survivors had a higher I-125 GFR prior to PICU admission (p = 0.045). A higher I-125 GFR prior to PICU admission among survivors may support this test's utility during SBT evaluation. In our experience, a high survival rate and freedom from RRT at the time of discharge support RRT use in the SBT population.

Background

Maintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential.

Methods

Survival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60,089 non-PKD and 1501 PKD MHD patients.

Results

PKD and non-PKD patients were 57±13 and 62±15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to <300 pg/mL (reference) had the lowest risk for mortality, the death risk was higher in patients with PTH<150 [hazard ratio (HR): 2.16 (95% confidence interval 1.53-3.06)], 300 to <600 [HR: 1.30 (0.97-1.74)] and ≥600 pg/mL [HR: 1.46 (1.02-2.08)], respectively. Similar patterns were found in non-PKD patients. Fully adjusted death HRs of time-averaged serum phosphorous increments<3.5, 5.5 to <7.5 and ≥7.5 mg/dL (reference: 3.5 to <5.5 mg/dL) for PKD patients were 2.82 (1.50-5.29), 1.40 (1.12-1.75) and 2.25 (1.57-3.22). The associations of alkaline phosphatase and calcium with mortality were similar in PKD and non-PKD patients.

Conclusion

Bone-mineral disorder markers exhibit similar mortality trends between PKD and non-PKD MHD patients, although some differences are observed in particular in low PTH and phosphorus ranges.

Interventional trials indicate adverse outcomes when hemoglobin >13 g/dL is targeted in patients with chronic kidney disease (CKD) who receive erythropoiesis-stimulating agents (ESAs). It is not clear whether high-achieved hemoglobin with minimal to no ESA administration as observed in some patients with polycystic kidney disease (PKD) is also associated with poor outcomes. Survival models were examined to assess the association between hemoglobin increments and mortality in a 6-year cohort of 2,402 PKD and 110,875 non-PKD hemodialysis patients across infrequent versus frequent ESA therapy defined as ESA < 25% of cohort time versus otherwise, respectively. Mortality risk was estimated by Cox proportional regression [hazard ratio (HR) and 95% of confidence interval] analysis. Patients with PKD were aged 58 ± 13 years and included 46% women 14% Blacks, respectively. Fully adjusted death HRs of time-averaged hemoglobin increments <11.0, 12.0 to <13.0 g/dL (reference: 11.0 to <12.0 g/dL) for frequent ESA therapy were 2.57 (1.48-4.48), 0.60 (0.43-0.82), and 0.81 (0.50-1.29), whereas for infrequent ESA therapy they were 1.33 (0.47-3.78), 0.28 (0.13-0.61), and 0.22 (0.09-0.57), respectively. Hence, in patients with PKD who require infrequent ESA, incrementally higher achieved hemoglobin including > 13.0 g/dL exhibits better survival; this incremental survival gain of higher hemoglobin is not observed in patients with PKD receiving frequent ESA administration, in whom hemoglobin concentration > 13 exhibits increased mortality.

Outcomes for pediatric SBT patients requiring perioperative RRT in the PICU remain unknown. The objectives were to document our center's experience with PICU SBT patients receiving perioperative RRT and to identify variables predictive of survival to discharge. A retrospective chart review of patients (ages, 0-18 yr) between January 1, 2000 and December 31, 2011 that received RRT within a SBT perioperative period and were transplanted at our university-affiliated, tertiary care children's hospital was performed. Six SBT patients received perioperative RRT (ages, 5-12 yr). Three patients (50%) survived to hospital discharge. Among survivors, RRT was required for a total of 1-112 days (mean, 49.7 days). All three survivors survived to hospital discharge without renal transplantation and free of RRT. There was a trend toward increased survival among older patients receiving RRT (p = 0.05). Survivors had a higher I-125 GFR prior to PICU admission (p = 0.045). A higher I-125 GFR prior to PICU admission among survivors may support this test's utility during SBT evaluation. In our experience, a high survival rate and freedom from RRT at the time of discharge support RRT use in the SBT population.

Purpose

Several observational studies have indicated that vitamin D receptor activators (VDRA), including paricalcitol, are associated with greater survival in maintenance hemodialysis (MHD) patients. However, patients with higher serum parathyroid hormone, a surrogate of higher death risk, are usually given higher VDRA doses, which can lead to confounding by indication and attenuate the expected survival advantage of high VDRA doses.

Methods

We examined mortality-predictability of low (>1 but <10 µg/week) versus high (≥10 µg/week) dose of administered paricalcitol over time in a contemporary cohort of 15 442 MHD patients (age 64 ± 15 years, 55% men, 44% diabetes, 35% African-Americans) from all DaVita dialysis clinics across the USA (7/2001-6/2006 with survival follow-ups until 6/2007) using conventional Cox regression, propensity score (PS) matching, and marginal structural model (MSM) analyses.

Results

In our conventional Cox models and PS matching models, low dose of paricalcitol was not associated with mortality either in baseline (hazard ratio (HR): 1.03, 95% confidence interval (CI): (0.97-1.09)) and (HR: 0.99, 95%CI:(0.86-1.14)) or time-dependent (HR: 1.04, 95%CI: (0.98-1.10)) and (HR: 1.12, 95%CI: (0.98-1.28)) models, respectively. In contrast, compared to high dose of paricalcitol, low dose was associated with a 26% higher risk of mortality (HR: 1.26, 95%CI: (1.19-1.35)) in MSM. The association between dose of paricalcitol and mortality was robust in almost all subgroups of patients using MSMs.

Conclusions

Higher dose of paricalcitol appears causally associated with greater survival in MHD patients. Randomized controlled trials need to verify the survival effect of paricalcitol dose in MHD patients are indicated.