Pre-transplant hypoalbuminemia is not associated with worse short-term outcomes among kidney transplant recipients.

INTRODUCTION: Serum albumin is an indicator of overall health status, but it remains unclear how pre-transplant hypoalbuminemia is associated with early post-transplant outcomes. METHODS: This study included all adult kidney transplant recipients (KTRs) at our center from 01/01/2001-12/31/2017 with serum albumin measured within 30 days before transplantation. KTRs were grouped based on pretransplant albumin level normal (≥4.0 g/dL), mild (≥3.5 - < 4.0g/dL), moderate (≥3.0 - < 3.5g/dL), or severe hypoalbuminemia (<3.0g/dL). Outcomes of interest included: length of hospital stay (LOS), readmission within 30 days, delayed graft function(DGF), and re-operation related to post-transplant surgical complications. We also analyzed rejection, graft failure, and death within 6 months post-transplant. RESULTS: A total of 2807 KTRs were included 43.6% had normal serum albumin, 35.3% mild, 16.6% moderate, and 4.5% severe hypoalbuminemia. Mild and moderate hypoalbuminemia were associated with a shorter LOS by 1.22 (p < 0.001) and 0.80 days (p = 0.01), respectively, compared to normal albumin. Moderate (HR: 0.58; 95% CI: 0.37-0.91; p = 0.02) and severe hypoalbuminemia (HR: 0.21; 95% CI: 0.07-0.68; p = 0.01) were associated with significantly lower rates of acute rejection within 6 months post-transplant. CONCLUSION: Patients with pre-transplant hypoalbuminemia have post-transplant outcomes similar to those with normal serum albumin, but with a lower risk of acute rejection based on the degree of hypoalbuminemia.

Risk factors and outcomes of BK viremia among deceased donor kidney transplant recipients based on donor characteristics.

INTRODUCTION: BK polyomavirus (BKV) is a common infection among kidney transplant recipients (KTR). Risk factors and outcomes based on donor characteristics remain largely unknown. METHODS: In this study, we aimed to analyze the impact of donor factors through a paired kidney analysis. We included 289 pairs of adult deceased donor transplants (578 KTRs total); each pair had received kidneys from the same donor. Recipient pairs were divided into three groups: "no BK group" if neither KTR developed BK viremia (n = 336), "discordant" if the only one did (n = 176), and "concordant" if both did (n = 66). Acute rejection (AR), graft failure, and BK nephropathy (BKN) were outcomes of interest. RESULTS: Donors in the concordant group were younger, had lower kidney donor profile index (KDPI), and were less likely to be donor after circulatory death (DCD). In multivariate analyses, KTRs who had a donor with a higher body mass index (BMI) (hazard ratio (HR): 0.97; 95% confidence interval (CI): 0.95-0.99; p = .009) were less likely to develop BKV. Concordance was not associated with AR (HR: 0.83; 95% CI: 0.51-1.34; p = .45), graft failure (HR: 1.77; 95% CI: 0.42-7.50; p = .43), or BKN (HR: 1.02; 95% CI: 0.51-2.03; p = .96). DISCUSSION: Our study suggests lower donor BMI is associated with BKV infection, and concordance or discordance between paired kidney recipients is not associated with poor outcomes.

Factors affecting sensitization following kidney allograft failure.

INTRODUCTION: Management of immunosuppression in a kidney transplant recipient with a failed allograft is complex; continuation carries infectious and metabolic risks, and discontinuation can lead to sensitization. METHODS: We evaluated risk factors for sensitization in 89 kidney or simultaneous kidney-pancreas recipients, whose kidney transplant failed after January, 2013 and who were subsequently re-evaluated for kidney transplantation. RESULTS: Among recipients with pre graft failure cPRA < 50%, calcineurin inhibitor (CNI) continuation (OR .11, P = .003) and steroid continuation (OR .17, P = .04) were associated with significantly lower odds of developing an absolute increase in cPRA of ≥50%. Each additional HLA mismatch was associated with OR of 2.16 (P = .02). CNI use was associated with OR of .09 (P = .001) for increase in cPRA to ≥80% if pre graft failure cPRA was <50%, and OR of .08 (P = .02) for increase in cPRA to ≥98% if pre graft cPRA was <80%. Anti-metabolites were continued more often among recipients who had a <50% increase (P = .006); however, the association was lost on multivariate analyses. Weaning off immunosuppression and higher number of HLA mismatches are associated with greater likelihood of sensitization. CONCLUSION: While both CNI and steroid continuation conferred some protection against increase in cPRA, CNI continuation was the only factor protecting against becoming highly sensitized.

Risk factors for progression from low level BK dnaemia to unfavorable outcomes after BK management via immunosuppressive reduction.

BACKGROUNDS: Effective management of BK viremia (BKPyV-DNAemia) in kidney transplant recipients (KTRs) involves regular monitoring and adjustment of immunosuppression. With this strategy, the majority of patients will clear BK or have ongoing, but non-significant, low-level BKPyV-DNAemia. However, despite adjustments, some will develop more severe sequelae of BK including BKPyV-DNAemia >5 log10 copies/mL and BK nephropathy, and others may develop de novo DSA (dnDSA) or acute rejection (AR). METHODS: This was a single-center study of KTRs transplanted at the University of Wisconsin-Madison between 01/01/2015 and 12/31/2017. In this study, we sought to elucidate characteristics associated with the progression of BKPyV-DNAemia to unfavorable outcomes after decreasing immunosuppressive medications for the management of BK viremia as described in consensus guidelines. RESULTS: A total of 224 KTRs fulfilled our selection criteria; 118 (53%) resolved or had persistent low DNAemia, 64 (28%) had severe BK/nephropathy, and 42 (19%) developed dnDSA or AR. In multivariable analysis, female gender (HR: 2.05; 95% CI: 1.08-3.90; P = .02); previous rejection (HR: 2.90; 95% CI: 1.04-8.12; P = .04), and early infection (HR: 0.81; 95% CI: 0.72-0.90; P < .001) were associated with the development of severe BK/nephropathy. Conversely, non-depleting induction at transplant (HR: 2.06; 95% CI: 1.03-4.11; P = .03), HLA mismatches >3 (HR: 2.27; HR: 1.01-5.06; P = .04), and delayed graft function (HR: 4.14; 95% CI: 1.12-15.28; P = .03) were associated with development of dnDSA and/or rejection. CONCLUSION: Our study suggests that almost half of KTRs with BKPyV-DNAemia managed by our immunosuppressant adjustment protocol progress unfavorably. Identification of these risk factors could assist the frontline clinician in creating an individualized immunosuppressive modification plan potentially mitigating negative outcomes.

Polyomavirus and cytomegalovirus infections are risk factors for grafts loss in simultaneous pancreas and kidney transplant.

BACKGROUND: Published literature on predictors of polyomavirus (BKV) and cytomegalovirus (CMV) infections in simultaneous pancreas and kidney (SPK) transplant and their impact on allograft outcomes remain sparse. We hypothesize that BKV and CMV viremia infections decrease allograft survival in SPK. Identifying modifiable predictors of BKV and CMV may help tailor immunosuppression and improve allograft survival. METHODS: All SPK recipients at our institution between January 2000 and April 2016 were included (n = 757). Thirty-nine recipients had BKV only and 25 had CMV only, and infection occurred at median follow-up times of 217 and 163 days, respectively. Event density sampling was used to match recipients with BKV or CMV to up to 10 recipients without infection by age, sex, and HLA mismatch status, and these were followed for a median of 4.3 years after infection. RESULTS: Older age (HR 1.49 for each decade; 95% CI: 0.95, 2.35; P = .083) and tacrolimus use (HR 20.6; 95% CI: 2.37, 179.53; P = .006) were associated with increased incidence of BKV, but not CMV, infection. Both BKV and CMV infections were associated with increased risk of allograft failure for both pancreas (BKV [HR 2.17; 95% CI 1.47, 3.208; P = .000], CMV [HR 1.7; 95% CI 1.077, 2.687; P = .023]) and kidney (BKV [HR 2.65; 95% CI 1.765, 3.984; P = .000], CMV [HR 2.07; 95% CI 1.295, 3.308; P = .002]). CONCLUSION: Older age at time of transplant and tacrolimus may help predict BKV infection in SPK recipients.

Mycophenolate Monotherapy in HLA-Matched Kidney Transplant Recipients: A Case Series of 20 Patients.

The ideal minimizing strategy for maintenance immunosuppression in HLA-matched kidney transplant recipients (KTR) is unknown. We hypothesized that mycophenolate (MPA) monotherapy is a safe and effective approach for maintenance therapy in this group of KTR. METHODS: Data were abstracted for 6-antigen HLA-matched KTR between 1994 and 2013. Twenty recipients receiving MPA monotherapy secondary to infection, cancer, calcineurin inhibitor (CNI) side effects, or immunosuppression minimization strategies were evaluated in this case series. RESULTS: MPA monotherapy had a low incidence of death-censored graft failure (3.19/100 person-y), rejection (0/100 person-y), hospitalization (1.62/100 person-y), malignancy (3.61/100 person-y), and infection (1.75/100 person-y). Further, 12-month mean or median serum creatinine (1.29 mg/dL), estimated glomerular filtration rate (64.3 mL/min/1.73 m2), urine protein creatinine ratio (143.2 mg/g), hemoglobin (13.9 g/dL), platelets (237.8 K/uL), and white blood cell count (9.04 K/uL) were favorable. There was a successful conversion rate of 90% (18 of 20) with 2 patients converting back to CNI-based regimens secondary to recurrence of membranous nephropathy and post-transplant lymphoproliferative disorder. CONCLUSIONS: Our findings indicate that MPA monotherapy may be a promising immunosuppression minimization strategy for HLA-matched KTR.

BK viremia is not associated with adverse outcomes in the absence of BK nephropathy.

There are limited data regarding the association of different levels of BK viremia and BK nephropathy (BKN), and graft outcomes. We studied the BK plasma PCR levels of all kidney transplant recipients (KTR) transplanted at our institution between 01/01/2006 and 06/30/2014. Patients were divided into groups based on their highest BK plasma PCR level within the first year following transplantation: undetectable, low (<1000 copies/mL), moderate (1000-10 000 copies/mL), high (>10 000-100 000 copies/mL), very high (>100 000 copies/mL), and those that had biopsy-proven BKN. There were a total of 1146 KTR during the study period: 813 with undetectable BK levels and 333 with any detectable BK level (87 with low, 79 with moderate, 88 with high, 34 with very high level BK, and 45 that had BKN). Compared to KTR with an undetectable BK level, incidence of mortality, graft failure, rejections,and infections were not significantly different for those with low, moderate, high, or very high BK level. Patients with BKN had a higher rate of infection and higher rates of total graft failure or death-censored graft failure compared to those with undetectable BK levels. BK viremia in the absence of BKN does not significantly increase the risk of rejection, infections, or graft failure compared to an undetectable BK level.

Nutritional value and chemical composition of Sudanese millet-based fermented foods as affected by fermentation and method of preparation.

BACKGROUND: Although kissra and hulu-mur are well known millet-based foods in Sudan, the effect of fer- mentation and methods of preparation on their chemical compositions has not been thoroughly investigated. The aim of this study was to investigate the method of preparation and the composition of kisra, and hulu-mur. METHODS: The effect of fermentation and method of preparation on the composition, and mi- crobiological load were examined in millet flour during the preparation of Sudanese fermented foods (kisra & hulu-mur). RESULTS: A significant (P < 0.05) difference in the composition of millet flour and millet-based fermented foods was observed. Protein was significantly increased as a result of fermentation, while oil and carbo- hydrates were decreased. Most minerals increased significantly after the addition of spices to the hulu-mur batter. The total amino acid in millet flour (97.98 g 100 g-1 protein) was influenced by fermentation and preparation method, as it decreased to 86.09 and 88.7 g 100 g-1 protein, in millet batter and kisra, respectively. CONCLUSIONS: Kisra, and hulu-mur were found to have apparent dietary qualities, in spite of some compounds being lost during their production.

Surfactant Protein A Expression in Chronic Rhinosinusitis and Atrophic Rhinitis

Introduction Surfactant protein A (SP-A) exhibits antimicrobial properties and interacts with a variety of respiratory tract pathogens. Objective The objective of this study was to detect the presence of SP-A and measure its alterations in chronic rhinosinusitis (CRS) and primary atrophic rhinitis (PAR) versus healthy controls. Methods Inferior turbinate and sinus mucosal biopsies were taken from 30 patients with CRS, 30 patients with PAR, and 20 healthy controls. Immunohistochemical staining for SP-A and polymerase chain reaction (PCR) amplification of SP-A messenger RNA were performed on nasal tissue samples. Results Immunostaining localized SP-A to the mucosa and submucosal glands in CRS specimens but failed to localize it in PAR specimens. Quantitative PCR showed a high, statistically significant increase in the SP-A levels of patients with CRS when compared with controls (p < 0.0001) and also demonstrated a significant reduction of SP-A in patients with PAR compared with controls (p < 0.005). Conclusion SP-A is significantly increased in CRS and decreased significantly in PAR and appears to be expressed by respiratory epithelial cells and submucosal glandular elements of the sinonasal mucosa. The potential therapeutic applications of surfactant in the enhancement of mucociliary clearance need to be studied. .

Surfactant protein a expression in chronic rhinosinusitis and atrophic rhinitis.

Introduction Surfactant protein A (SP-A) exhibits antimicrobial properties and interacts with a variety of respiratory tract pathogens. Objective The objective of this study was to detect the presence of SP-A and measure its alterations in chronic rhinosinusitis (CRS) and primary atrophic rhinitis (PAR) versus healthy controls. Methods Inferior turbinate and sinus mucosal biopsies were taken from 30 patients with CRS, 30 patients with PAR, and 20 healthy controls. Immunohistochemical staining for SP-A and polymerase chain reaction (PCR) amplification of SP-A messenger RNA were performed on nasal tissue samples. Results Immunostaining localized SP-A to the mucosa and submucosal glands in CRS specimens but failed to localize it in PAR specimens. Quantitative PCR showed a high, statistically significant increase in the SP-A levels of patients with CRS when compared with controls (p < 0.0001) and also demonstrated a significant reduction of SP-A in patients with PAR compared with controls (p < 0.005). Conclusion SP-A is significantly increased in CRS and decreased significantly in PAR and appears to be expressed by respiratory epithelial cells and submucosal glandular elements of the sinonasal mucosa. The potential therapeutic applications of surfactant in the enhancement of mucociliary clearance need to be studied.

Antithymocyte globulin is associated with a lower incidence of de novo donor-specific antibodies in moderately sensitized renal transplant recipients.

BACKGROUND: Recent evidence suggests that de novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and graft failure after kidney transplantation. The effects of induction immunosuppression on dnDSA are unknown. METHODS: The study population comprised 114 consecutive moderately sensitized (positive DSA and negative flow crossmatch) recipients who received deceased donor renal transplants between December 2009 and November 2011. Patients were divided into two groups based on induction immunosuppression: antithymocyte globulin (ATG) (n=85) or basiliximab (n=29) and were followed up for 36 months. RESULTS: Patients in the ATG group received a mean dose of 4.98 mg/kg ± 7.9 mg/kg, had a significantly higher PRA, and received more plasmapheresis and IVIG at the time of transplant. The incidence of dnDSA (P=0.02, HR=0.33, 95% CI 0.09-1.24) and ABMR (P=0.002, HR=0.2, 95% CI 0.04-0.87) was significantly lower in the ATG group. In multivariate regression analyses, ATG induction was the single most important variable associated with both ABMR and dnDSA. CONCLUSIONS: In moderately sensitized deceased donor renal transplant recipients, induction with ATG is associated with a reduction in the occurrence of dnDSA and ABMR when compared with basiliximab.

Post-transplant DSA monitoring may predict antibody-mediated rejection in sensitized kidney transplant recipients.

We examined whether changes in posttransplant highest intensity donor specific anti-HLA antibody specificity (DSAmax) measured by single antigen bead via Luminex (One Lambda, Inc.) were associated with antibody-mediated rejection (AMR). We conducted a retrospective analysis examining risk factors for AMR in 116 consecutive patients who underwent desensitization between 1/1/2009 and 9/1/2010. All patients had a negative flow cytometry crossmatch. The mean patient age at transplant was 46.4 +/- 4 years. The mean peak PRA (panel reactive antibody) and DSAmax at transplant were 40 +/- 6% and 894 +/- 150 mean fluorescent intensity (MFI), respectively. The mean time to rejection was 1.5 +/- 0.4 months. Cox regression analyses demonstrated that an increase in DSAmax by one week after transplant was significantly associated with AMR (pure or mixed). A rise in DSAmax greater than 500 MFI at 1 week was associated with a 2.6 times greater risk of rejection (HR 2.6, 95% CI 1.1 - 6.3, p = 0.02). We conclude that a rise in DSAmax at one week is an independent risk factor forAMR and that posttransplant DSA monitoring strategies may reduce the risk of AMR in sensitized patients.

Renin angiotensin system inhibition in the older person: a review.

The efficacy and safety of rennin angiotensin system (RAS) inhibition for lowering blood pressure in older populations has been demonstrated in a number of clinical trials. Whether a patient's age influences the overall ability of these drugs to lower blood pressure and protect against progress of cardiovascular and kidney disease has been the focus of few clinical trials. Herein, the author's review the mechanism of action of the renin angiotensin cascade and then discuss the clinical evidence surrounding the use of RAS-blocking drugs in the older population.