Individual Histologic Lesions and Composite Scores in Implant Biopsies Affect Short-Term and Long-Term Kidney Allograft Function.

OBJECTIVES: Our aim was to evaluate which histologic lesions in a donor kidney were associated with graft function up to 5 years and with its dynamics. MATERIALS AND METHODS: We retrospectively investigated the association between acute and chronic individual histologic lesions and composite scores in preimplant and postreperfusion biopsies from deceased-donor (n = 101) and living-donor (n = 29) kidneys with initial graft function and function at discharge, at 6 months, and at 5 years and slopes of estimated glomerular filtration rate from discharge to 6 months and from 6 months to 5 years. RESULTS: A high frequency of chronic and acute histologic lesions in donor kidneys is characteristic of our population of donors with high cardiovascular risk. Glomerulitis in preimplant biopsies predicted delayed graft function. Arteriolar hyalinosis predicted impaired initial graft function. Arteriolar hyalinosis and arteriosclerosis both predicted lower estimated glomerular filtration rate at discharge and ≥ 25% drop in function after 6 months. Glomerulosclerosis affected the estimated glomerular filtration rate at discharge and at 6 months; percentage of changed glomeruli predicted lower function at discharge and at 5 years. Glomerular thrombi in preimplant and postreperfusion biopsies predicted negative slope in estimated glomerular filtration rate from discharge to 6 months and a ≥ 25% drop in function after 6 months, respectively. Fibrinoid necrosis in glomeruli in preimplant biopsies predicted decline in function of ≥ 5 mL/min/1.73m² every year after 6 months. Chronic and total preimplant and posttransplant Banff scores predicted lower estimated glomerular filtration rate at discharge and at 6 months, with ≥ 25% drop in function after 6 months. CONCLUSIONS: Intraoperative biopsies are important in identifying patients at risk for worse graft function, especially concerning absence of gain of function early after transplant and loss of function late after transplant.

High urinary interleukin-2 in late post-transplant period portends a risk of decline in kidney allograft function: a preliminary study.

BACKGROUND: Predictive factors for the rate of decline in kidney allograft function beyond the first post-transplant year have not been thoroughly studied. We aimed to determine whether a single measurement of serum and urinary interleukin 2, interleukin 8 and interleukin 10 at 1-15 years after kidney transplantation could predict a decline in estimated glomerular filtration rate (eGFR) over a 2-year period. RESULTS: Greater serum concentrations of interleukin 8 and interleukin 10 in 30 recipients of kidney allograft at enrollment were associated with lower eGFR after 1 year (beta = - 0.616, p = 0.002 and beta = - 0.393, p = 0.035, respectively), whereas serum concentrations of interleukin 8 also demonstrated significant association with eGFR after 2 years of follow-up (beta = - 0.594, p = 0.003). Higher urinary interleukin 2 concentrations were associated with lower eGFR at baseline (rho = - 0.368, p = 0.049) and after the first (beta = - 0.481, p = 0.008) and the second year (beta = - 0.502, p = 0.006) of follow-up. Higher urinary interleukin 2 concentrations predicted certain decline in eGFR of ≥ 25% from baseline after 1 year of follow-up in logistic regression: odds ratio = 2.94, confidence interval 1.06-8.18, p = 0.038. When combined with time after transplantation, urinary interleukin 2 demonstrated good accuracy in predicting rapid decline in eGFR by > -5 mL/min/1.73 m2/year (area under the receiver-operator characteristic curve: 0.855, confidence interval 0.687-1.000, and p = 0.008). CONCLUSIONS: Our findings suggest that urinary interleukin 2 in the late period after kidney transplantation has promise in identifying patients who are at risk for progressive loss of graft function in a short-time perspective and need closer monitoring.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

BACKGROUND: We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. METHODS: Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. RESULTS: We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. CONCLUSIONS: Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

High Urinary Aspartate Aminotransferase in the Late Posttransplant Period Predicts Rapid, Progressive Decline in Kidney Allograft Function.

OBJECTIVES: Scant information is available on factors for predicting the rate of decline in kidney allograft function beyond 1 year posttransplant.We investigated whether urinary enzymes (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, N-acetyl-ß-D-hexosaminidase, and ε-glutamyl transpeptidase) in the late postoperative period can predict the decline in estimated glomerular filtration rate. MATERIALS AND METHODS: In 79 kidney allograft recipients 1 to 17 years after kidney transplant, we assessed a value of urinary enzymes single measurement for predicting the slope of estimated glomerular filtration rate, rapid decline in estimated glomerular filtration rate (> 5 mL/min/1.73 m² /y), and significant decline in estimated glomerular filtration rate (≥ 25% from baseline) during a 2-year period. RESULTS: At baseline, patients with estimated glomerular filtration rate < 60 mL/min/1.73 m² (n = 54) differed from those with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m² (n = 25) only in their lower median urinary alanine aminotransferase:creatinine ratio (expressed as U/L:mmol/L): 0.055 versus 0.222 (P = .011). Higher urinary activity of aspartate aminotransferase at baseline predicted the negative-slope value for estimated glomerular filtration rate (beta, -0.279; standard error, 0.131; P = .037) and decline in estimated glomerular filtration rate of > 5 mL/min/1.73 m ²/year (odds ratio, 2.06; 95% confidence interval, 1.10-3.83; P = .023) over 2 years. It also predicted the drop in estimated glomerular filtration rate ≥ 25% after 1 year (odds ratio, 2.62; 95% confidence interval, 1.07-6.37; P = .034) and 2 years (odds ratio, 2.75; 95% confidence interval, 1.12-6.73; P =.027). Combined with time after transplant, urinary aspartate aminotransferase had good power for predicting an estimated glomerular filtration rate decrease ≥ 25% after 2 years of follow-up. CONCLUSIONS: Higher urinary activity of aspartate aminotransferase in the late posttransplant period is useful for identifying transplant patients who are at risk for progressive loss of graft function.

Plasma Brain-Derived Neurotrophic Factor as a Biomarker for the Main Types of Mild Neurocognitive Disorders and Treatment Efficacy: A Preliminary Study.

Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer's disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy.

High Serum Level of ß2-Microglobulin in Late Posttransplant Period Predicts Subsequent Decline in Kidney Allograft Function: A Preliminary Study.

BACKGROUND: Identification of patients at risk for kidney allograft (KAG) failure beyond the first posttransplant year is an unmet need. We aimed to determine whether serum beta-2-microglobulin (ß2MG) in the late posttransplant period could predict a decline in KAG function. METHODS: We assessed a value of single measurement of serum ß2MG at one to seventeen years after transplantation in predicting the estimated glomerular filtration rate (eGFR) and the decline in eGFR over a period of two years in 79 recipients of KAG. RESULTS: At baseline serum ß2MG concentration was higher (P = 0.011) in patients with allograft dysfunction: 8.67 ± 2.48 µg/mL versus those with satisfactory graft function: 6.67 ± 2.13 µg/mL. Higher ß2MG independently predicted the lower eGFR, the drop in eGFR by ≥25% after one and two years, and the value of negative eGFR slope. When combined with proteinuria and acute rejection, serum ß2MG had excellent power in predicting certain drop in eGFR after one year (AUC = 0.910). In conjunction with posttransplant time serum ß2MG had good accuracy in predicting certain eGFR drop after two years (AUC = 0.821). CONCLUSIONS: Elevated serum ß2MG in the late posttransplant period is useful in identifying patients at risk for rapid loss of graft function.