Nascent chains derived from a foldable protein sequence interact with specific ribosomal surface sites near the exit tunnel.

In order to become bioactive, proteins must be translated and protected from aggregation during biosynthesis. The ribosome and molecular chaperones play a key role in this process. Ribosome-bound nascent chains (RNCs) of intrinsically disordered proteins and RNCs bearing a signal/arrest sequence are known to interact with ribosomal proteins. However, in the case of RNCs bearing foldable protein sequences, not much information is available on these interactions. Here, via a combination of chemical crosslinking and time-resolved fluorescence-anisotropy, we find that nascent chains of the foldable globin apoHmp1-140 interact with ribosomal protein L23 and have a freely-tumbling non-interacting N-terminal compact region comprising 63-94 residues. Longer RNCs (apoHmp1-189) also interact with an additional yet unidentified ribosomal protein, as well as with chaperones. Surprisingly, the apparent strength of RNC/r-protein interactions does not depend on nascent-chain sequence. Overall, foldable nascent chains establish and expand interactions with selected ribosomal proteins and chaperones, as they get longer. These data are significant because they reveal the interplay between independent conformational sampling and nascent-protein interactions with the ribosomal surface.

Hypoalbuminemia is a risk factor for invasive fungal infections and poor outcomes in infected kidney transplant recipients.

INTRODUCTION: Invasive fungal infections (IFI), are estimated to occur in 2%-14% of kidney transplant recipients (KTRs) in the current era of immune suppression and are associated with high mortality rates. We hypothesized that hypoalbuminemia in KTRs is a risk factor for IFI and would be associated with poor outcomes. METHODS: In this study, using data from a prospective cohort registry, we describe the frequency of IFI due to Blastomycosis, Coccidioidomycosis, Histoplasmosis, Aspergillosis, and Cryptococcus in KTRs with serum albumin levels measured 3-6 months before diagnosis. Controls were selected based on incidence density sampling. KTRs were divided into three groups based on the pre-IFI serum albumin level: normal (≥4 g/dL), mild (3-4 g/dL), or severe (<3 g/dL) hypoalbuminemia. Outcomes of interest were uncensored graft failure after IFI and overall mortality. RESULTS: A total of 113 KTRs with IFI were compared with 348 controls. The incidence rate of IFI among individuals with normal, mild, and severe hypoalbuminemia was 3.6, 8.7, and 29.3 per 100 person-years, respectively. After adjustment for multiple variables, the trend for risk of uncensored graft failure following IFI was greater in KTRS with mild (HR = 2.1; 95% CI, .75-6.1) and severe (HR = 4.47; 95% CI, 1.56-12.8) hypoalbuminemia (P-trend < .001) compared to those with normal serum albumin. Similarly, mortality was higher in severe hypoalbuminemia (HR = 1.9; 95% CI, .67-5.6) compared to normal serum albumin (P-trend < .001). CONCLUSION: Hypoalbuminemia precedes the diagnosis of IFI in KTRs, and is associated with poor outcomes following IFI. Hypoalbuminemia may be a useful predictor of IFI in KTRs and could be incorporated into screening algorithms.

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.

Serum Albumin Level Before Kidney Transplant Predicts Post-transplant BK and Possibly Cytomegalovirus Infection.

INTRODUCTION: Opportunistic viral infections cause extensive morbidity and mortality in kidney transplant recipients (KTRs). Low serum albumin levels before and after transplant have been associated with negative outcomes. However, it is uncertain whether serum albumin levels before transplantation are associated with the risk for post-transplantation opportunistic BK polyomavirus (BKV) or cytomegalovirus (CMV). METHODS: We reviewed all KTRs transplanted at our institution between 1 January 2005 and 31 December 2015 with serum albumin measured within 45 days before transplantation in a retrospective observational cohort study. Selected patients were stratified into 3 groups: normal albuminemia (≥3.5 g/dl), moderate hypoalbuminemia (3.49-2.5 g/dl), and severe hypoalbuminemia (<2.5 g/dl). Patients were observed for post-transplantation BKV or CMV according to standard of care. RESULTS: We included 1717 patients in this study; 72.3% had normal serum albumin, 26.3% had moderate hypoalbuminemia, and 1.5% had severe hypoalbuminemia. Moderate and severe hypoalbuminemia incurred a higher risk for BKV compared with normal serum albumin levels in univariable analysis (moderate hypoalbuminemia: hazard ratio [HR] = 1.5; 95% confidence interval [CI], 1.14-1.90; P = .003); severe hypoalbuminemia: HR = 2.15; 95% CI, 1.01-4.56; P = 0.05). Although not significant after multivariable adjustment, there was still 18% increased risk in moderate hypoalbuminemia and 64% in severe hypoalbuminemia for BKV compared with the normal albumin group. Moderate hypoalbuminemia was associated with a higher risk for CMV infection than normal serum albumin levels in multivariable analysis, although it was not statistically significant (HR = 1.15; 95% CI, 0.36-3.64; P = 0.81). CONCLUSIONS: These findings suggest that pretransplantation hypoalbuminemia is associated with a higher risk for post-transplantation BKV and possibly CMV. More intense screening is warranted for these viruses in recipients with pretransplant hypoalbuminemia.