Calciphylaxis in uraemic and nonuraemic settings: clinical risk factors and histopathological findings.

BACKGROUND: Calciphylaxis is a life-threatening cutaneous ulcerative/necrotic disease characterized by vascular calcification/occlusion. It occurs most commonly in end-stage kidney disease (ESKD), known as uraemic calciphylaxis (UC) but can also occur in patients with chronic kidney disease (CKD) and normal kidney function (nonuraemic calciphylaxis; NUC). There are few large series of NUC in the literature. AIM: To compare the clinicopathological features of UC and NUC. METHODS: We retrospectively compared the clinicopathological features of 35 patients with NUC during the period 2010-2020 with those of 53 patients with UC (control group). Cases were classified as NUC in the absence of all of the following: ESKD, significant CKD (defined as serum creatinine > 3 mg/dL or creatinine clearance < 15 mL/min) and acute kidney injury requiring kidney replacement therapy or kidney transplantation. RESULTS: NUC represented 40% of the total cases, and there was a higher number of women (P < 0.01) and a higher median body mass index (P = 0.06) compared with the control UC group. Elevated parathyroid hormone was present in 44% of patients with NUC. Most of the tested patients were positive for lupus anticoagulants (56%). NUC biopsies showed a higher rate of extravascular calcium deposits (73% vs. 47%, P = 0.03). Dermal reactive vascular proliferation was the most common dermal change (32%). CONCLUSIONS: NUC is more common than previously reported and shows a higher predilection for obese postmenopausal women. Undiagnosed hyperparathyroidism shows a possible association with NUC. Lupus anticoagulants were positive in most patients. NUC biopsies are more likely than UC biopsies to display extravascular calcium deposition.

Risk factors for retransplant kidney recipients: relisting and outcomes from patients' primary transplant.

As of November 2013, 14.5% of the waitlist for a donor kidney comprised patients awaiting a retransplant. We performed a retrospective cohort study of 11,698 adult solitary kidney recipients using national Scientific Registry of Transplant Recipients data transplanted between 2002 and 2011. The aim was to investigate whether outcomes from patients' initial transplants are significant risk factors for patients' repeat transplants or for likelihood of relisting after a failed primary transplant. Retransplant recipients were more likely to be treated for acute rejection [adjusted odds ratio (AOR), 95% confidence interval (CI) = 1.26 (1.07-1.48), p = 0.0053] or hospitalized (AOR = 1.19, 95% CI 1.08-1.31, p = 0.0005) within a year of retransplantation if these outcomes were experienced within a year of primary transplant. Delayed graft function following primary transplants was associated with 35% increased likelihood of recurrence (AOR = 1.35, 95% CI = 1.18-1.54, p < 0.0001). An increase in 1-year GFR after primary transplant was associated with GFR 1 year postretransplant (ß = 6.82, p < 0.0001), and retransplant graft failure was inversely associated with 1-year primary transplant GFR (adjusted hazard ratio = 0.74, 95% CI = 0.71-0.76 per 10 mL/min/1.73 m(2) ). A decreased likelihood for relisting was associated with hospitalization and higher GFR following primary transplantation. The increasing numbers of individuals requiring retransplants highlights the importance of incorporating prior transplant outcomes data to better inform relisting decisions and prognosticating retransplant outcomes.

Association of metabolic syndrome with kidney function and histology in living kidney donors.

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m(2) instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novo metabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

Beneficial outcomes of a steroid-free regimen with thymoglobulin induction in pancreas-kidney transplantation.

BACKGROUND: Steroid-free immunosuppressive regimens are becoming more common in pancreas transplantation, with persistent concerns regarding its safety and efficacy. METHODS: We performed a retrospective chart review of 87 pancreas transplant recipients-22 simultaneous pancreas-kidney transplants, 48 pancreas-after-kidney transplants, and 17 pancreas transplant alone-who underwent transplantation within the period of January 2000 to November 2006 and who received induction therapy with thymoglobulin followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil. We compared one group on a steroid-free regimen (n = 25) with another on a steroid-based regimen (n = 62). RESULTS: At 6 months, there was no kidney graft loss and no significant difference between groups (steroid-free vs steroid-based groups) in patient survival (100% vs 96.8%), pancreas graft survival (96.0% vs 93.5%), acute rejection (4.0% vs 11.3%), hospitalization for any cause (60.0% vs 51.6%), infection requiring hospitalization (16.0% vs 32.3%), or incidence of BK viremia (0% vs 3.2%). CMV viremia occurred less in the steroid-free group (0% vs 17.7% in the steroid-based group, P = .024). The estimated glomerular filtration rate (eGFR) at 6 months was higher in the steroid-free group (74.8 vs 55.7 mL/min/1.73 m2 in the steroid-based group, P = .001), with fewer occurrences of a 25% decline in eGFR (33.3% among the steroid-free group vs 61.7% among steroid-based group, P = .019), despite similar average tacrolimus exposure (11.7 +/- 3.7 vs 12.2 +/- 2.7 ng/dL, P = .478). CONCLUSIONS: A steroid-free regimen with thymoglobulin induction followed by tacrolimus and mycophenolate mofetil for maintenance in pancreas transplantation was safe and effective in preventing rejection, with reduced incidence of CMV infection and better-preserved kidney function.

Prevalence and clinical course of BK virus nephropathy in pancreas after kidney transplant patients.

The influence of BK virus nephropathy (BKVN) in pancreas after kidney (PAK) transplantation is unclear. A retrospective analysis of PAK transplants performed at our center was conducted to determine the impact of BKVN. Among 40 PAK transplants performed using sequential immunosuppression, four patients developed BKVN, as defined by a >20% rise in serum creatinine and BK viremia (BK plasma load >4 log copies/mL), at a median of 19 months following PAK. In all four patients, treatment of BKVN consisted of reduction in tacrolimus, cessation of mycophenolate mofetil, and introduction of leflunomide. With this approach, two patients experienced improvement or stabilization of renal function. The remaining two patients progressed to dialysis dependence despite treatment. Plasma BK load < or =5 log copies/mL was associated with graft preservation. Gender, age, delay between transplants, cumulative Thymoglobulin dose, and type of kidney donor were not associated with BK virus infection. Pancreas graft rejection or dysfunction was not observed with the above immunosuppression modification. Mean amylase and lipase > or =6 months following BKVN treatment remained normal. BKVN is an important cause of kidney allograft loss in PAK patients. Screening and early treatment of BKVN may enable preservation of kidney and pancreas grafts.

Donor kidney volume and outcomes following live donor kidney transplantation.

Pre-donation kidney volume and function may be crucial factors in determining graft outcomes in kidney transplant recipients. We measured living donor kidney volumes by 3D helical computed tomography scanning and glomerular filtration rate (GFR) by (125)I-iothalamate clearances in 119 donors, and correlated these values with graft function and incidence of acute rejection at 2 years post-transplantation. Kidney volume strongly correlated with GFR (Pearson r= 0.71, p < 0.001). Body size and male gender were independent correlates of larger kidney volumes, and body size and age were predictors of kidney function. The effects of transplanted kidney volume on graft outcome were studied in 104 donor-recipient pairs. A transplanted kidney volume greater than 120 cc/1.73 m(2) was independently associated with better estimated GFR at 2 years post-transplant when compared to recipients of lower transplanted kidney volumes (64 +/- 19 vs. 48 +/- 14 mL/min/1.73 m(2), p < 0.001). Moreover, recipients of lower volumes had a higher incidence of acute cellular rejection (16% vs. 3.7%, p = 0.046). In conclusion, kidney volume strongly correlates with function in living kidney donors and is an independent determinant of post-transplant graft outcome. The findings suggest that (1) transplantation of larger kidneys confers an outcome advantage and (2) larger kidneys should be preferred when selecting from otherwise similar living donors.

Incidence trends and mortality in end-stage renal disease attributed to renovascular disease in the United States.

End-stage renal disease (ESRD) attributed to renovascular disease (RVD-ESRD) has been incompletely characterized. We determined incidence trends, clinical features, prior treatment, and survival of patients with RVD-ESRD using the US Renal Data System database. Primary causes of ESRD were assessed in patients starting ESRD therapy during 1991 to 1997. The incidence of RVD-ESRD increased from 2.9/10(6) per year (1.4% of new ESRD cases) to 6.1/10(6) per year (2.1%). The annualized increase was 12.4% per year. This is a greater rate of increase than for ESRD from diabetes mellitis (DM-ESRD; 8.3% per year) and ESRD overall (5.4% per year). The risk for RVD-ESRD versus other-cause ESRD correlated positively with age (odds ratio [OR], 1.7 per 10-year increment; P < 0.0001) and male sex (OR, 1.2; P < 0.0001) and negatively with black (OR, 0.17; P < 0.0001), Asian (OR, 0.29; P < 0.0001), and Native American race (OR, 0.31; P < 0.0001). The unadjusted prevalence of coronary heart disease, cerebrovascular disease, and peripheral vascular disease was greater in patients with RVD-ESRD versus other-cause ESRD (P < 0.001). Of patients with RVD-ESRD, 5% underwent revascularization in the 2 years before ESRD compared with 0.5% of patients with other-cause ESRD, including DM-ESRD. Adjusted for age, race, sex, comorbidity, and laboratory values, the survival of patients with RVD-ESRD was similar to that for patients with other-cause ESRD (risk ratio, 1.01; P = 0.5). These findings suggest that RVD-ESRD is increasing faster than other-cause ESRD and is not independently associated with an increased mortality risk. Strategies may exist to prevent progression to ESRD and merit priority for further study.

Ultrasound detection of microembolic signals in hemodialysis accesses.

Microembolic signals (MES) detected by ultrasound, thought to be of gaseous or solid origin, have been described with decompression illness and in the intracranial and cardiopulmonary circulation. We describe the first reported cases of MES occurring in hemodialysis accesses. Two hemodialysis patients, one with a synthetic graft and one with an arteriovenous fistula, showed MES during a dialysis session detected by duplex ultrasound. We postulate that these MES represent cavitation bubbles developing from turbulent blood flow around the venous needle in the access. However, other potential causes exist, including air introduced into the circulation from the dialysis circuit or microemboli arising from thrombus or atheroma.

Regulation of usage of membrane and secreted 3' termini of alpha mRNA differs from mu mRNA.

Previous studies demonstrated that the addition of transforming growth factor-beta (TGF-beta) to LPS-stimulated B cell cultures induced cells to express membrane IgA and to mature to IgA-secreting cells without a parallel change in usage of 3' termini by alpha mRNA. In these cultures, the secreted form of alpha mRNA was predominant even before expression of membrane IgA could be detected. In the present study, we demonstrate that the preferential usage of the secreted terminus of alpha mRNA in these cultures is not caused by transcription termination and reflects a difference in the regulation of choice of 3' terminus for alpha and mu mRNA. The addition of TGF-beta to LPS-stimulated cultures causes an increase in the steady state level of alpha mRNA using the secreted 3' terminus. In contrast, TGF-beta decreases the steady state level of mu mRNA and inhibits usage of the 3' terminus for the secreted form of mu, suggesting that the choice of 3' terminus for alpha and mu mRNA is regulated differently in LPS-stimulated cultures. To determine whether the difference in usage of 3' termini by alpha and mu mRNA was a property of the culture system or whether it reflected a difference in regulation, C alpha was transfected into cell lines representing different stages of B cell development. The secreted form of alpha mRNA predominates regardless of the ratio of membrane to secreted forms of the endogenous C mu gene. A similar dichotomy in 3' terminus usage occurred in a stable C alpha transfectant of the BCL1 lymphoma, suggesting that trans-acting factors are not limiting. Furthermore, as was the case with normal B cells, the predominance of the secreted form of the transfected C alpha genes was not due to transcription termination. These data demonstrate that usage of 3' terminus in alpha and mu mRNA is regulated differently.