Serum Cystatin C and β2-Microglobulin as Markers of Glomerular Filtration Rate

Continuous efforts have been made to find out precise and simple method for determination of glomerular filtration rate (GFR). Cystatin C (cysteine proteinase inhibitor = CyC) is a low molecular weight (LMW) protein which is produced constantly by all nucleated cells independently of different pathological conditions and eliminated from the blood exclusively by glomeruli. So, CyC closely reflects the GFR. In the present study 75 patients aged between 18 and 74 (44.3 ± 12.2) years were analyzed, with the aim to compare the reciprocal values of serum level of LMW proteins CyC and β₂-microglobulin (β₂-MG) with creatinine clearance (Ccr) as a measure of GFR. Patients were divided into groups according to sex, age (<60; >60 years) and renal diseases: patients with glomerulonephritis (GN) with and without nephrotic proteinuria, pyelonephritis (PyN), and renal transplant (Tx). High correlation between Ccr and 1/CyC (r = 0.81; p<0.01) and Ccr and 1/β₂-MG (r = 0.80; p<0.01) in all examined patients was found. There was significant correlation between Ccr and 1/CyC (0.82 vs. 0.79) and Ccr and 1/β₂-MG (0.85 vs. 0.76) in men as well in women, and also in two groups of patients formed according to the age (0.82 vs. 0.77; p<0.01; 0.80 vs. 0.81; p<0.01), without any statistical significant difference between the groups. In studied groups with different renal diseases, there were no differences in correlation coefficients between Ccr and 1/CyC and Ccr and 1/β₂-MG (p1 = 0.29; p2 = 0.21; p3 = 0.79; p4 = 0.43), without statistical differences between the groups, except significant difference in correlation coefficients for Ccr and 1/β₂-MG between patients with GN with and without nephrotic proteinuria (p<0.032). LMW proteins, serum CyC and β₂-MG, are as good markers of GFR as Ccr, regardless sex and age. Both of these LMW proteins are good markers of GFR in patients with GN without nephrotic proteinuria, PyN and Tx patients. In patients with GN and nephrotic proteinuria serum CyC is a better marker of GFR than β₂-MG.     

Is Cyctatin C Valuable Marker of Glomerular Filtration Rate in Living Kidney Donors After Uninephrectomy?

BackgroundThe determination of kidney function plays a pivotal role in living donors renal assessment because of the long-term hazards of life with one kidney. Guidelines recommend estimation of glomerular filtration rate (GFR) by the Modification of Renal Disease (MDRD) or Cockroft-Gault equations for people with normal or near-normal renal function. Cystatin C (CysC) has been introduced as an alternative endogenous marker of GFR.ObjectiveThe objective of the study was to evaluate residual renal function among living kidney donors by comparing serum CysC concentrations and estimated GFR according to the MDRD formula or the Cockroft-Gault equation.Patients and methodsForty living kidney donors showed a mean age of 46.14 years. Their GFR was estimated according to the abbreviated MDRD (aMDRD) and Cockroft-Gault formula adjusted for body surface area. Twenty-two donors underwent diethylenetriaminepentaacetic acid (DTPA) renal studies. Serum CysC concentrations were measured during the last follow-up visit. GFR values according to Cockroft-Gault formula and MDRD formula were correlated with CysC concentrations using Pearson's linear correlation.ResultsMean GFR according to the aMDRD formula and Cocroft-Gault formula decreased after nephrectomy. The Cockroft-Gault formula overestimated the DTPA GFR in our study. No significant differences were observed between DTPA GFR and GFR estimated using the aMDRD equation. The rate of GFR decrease was approximately 0.8 mL/min/1.73m² per year. No significant correlation was observed between serum CysC concentration and GFR. Microalbuminuria was observed in one patient after nephrectomy.ConclusionsaMDRD equation to estimate GFR is more precise than Cockroft-Gault formula and cystatin C in living kidney donors after nephrectomy and should be preferred model in these patients.     

Adverse Outcomes of Tacrolimus Withdrawal in Immune–Quiescent Kidney Transplant Recipients

Concerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor–reactive IFN-γ ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria.     

Nonverbal Communication and Psychopathology in Kidney Transplant Recipients

Transplant recipients have difficulty expressing, identifying, and describing their emotional experiences. The Machover human figure test allows us to bring out the deepest contents of a patient's personality, which are normally hidden and not explained to structured quantitative tests. The study analyzed possible situations of distress and possible symptoms of psychopathology in kidney transplant recipients, emerged from the projective test of the human figure and not easily verbalized to the common standardized tests.The sample included 80 kidney transplant patients (51 men and 29 women; mean age, 47.74 [SD, 12.39] years) during follow-up visits at 12 months after transplant. The Machover test was used to evaluate body image, affective aspects, and personality variables by projective method; the Symptom Checklist-90-R was used for the evaluation of possible psychopathology, and the 36-Item Short Form Health Survey was used for the assessment of perceived quality of life.Resultsshowed that the more anxiety there is in the human figure test, the less somatization dimensions (ANX/SOM R = ?331, P < .05), depression (ANX/DEP R = ?326, P < .05), and the global index of psychic symptomatology (ANX/GSI R = ?367, P < .05) of the Symptom Checklist-90-R are present.This research has confirmed the hypothesis that the spontaneous graphic production of the recipients, through the projective methods, allows them to identify and deepen their psychological contents and to activate and maintain a good psychophysical balance post transplant.     

Kidney Transplant Recipients With Rheumatic Diseases: Epidemiological Data From the Polish Transplant Registries 1998–2015

Chronic kidney disease (CKD) is a common complication of rheumatic disorders. We analyzed the incidence of different rheumatic conditions as a primary diagnosis of end-stage renal disease (ESRD) in kidney transplant recipients in Poland.Data were received from the national waiting list for organ transplantation (Poltransplant) registries. Primary diagnosis leading to ESRD were analyzed in 15,984 patients who received kidney transplants between 1998 and 2015. There was no information about primary diagnosis in 4981 cases (31%) and in 1482 cases (9%) the diagnosis was described as unknown.Rheumatic diseases were specified in 566 (5.14%) kidney transplant recipients: lupus erythematosus, (systemic lupus erythematous nephritis) in 211 (1.92%), vasculitis in 176 (1.60%), amyloidosis AA in 82 (0.75%), hemolytic uremic syndrome in 59 (0.54%), secondary glomerulonephritis in 24 (0.22%), scleroderma in 9 (0.08%), rheumatoid arthritis in 4 (0.04%) and Sjögren syndrome in 1 (0.01%). Graft survival at 1 and 5 years were significantly better in the nonrheumatic versus rheumatic group (90 vs 87% and 76 vs 72% respectively, P = .04). Recipient survival at 5 years was significantly better in the nonrheumatic versus the rheumatic group (88 vs 84%, P = .02).Our study showed that systemic lupus erythematosus and systemic vasculitides are the major rheumatic causes of ESRD in the Polish population. Long-term graft and recipient survival were significantly better in the nonrheumatic versus the rheumatic group in the Poltransplant cohort.     

Clinical Significance of C3d Assay in Kidney Transplant Recipients With Donor-Specific Anti–Human Leukocyte Antigen Antibodies

BackgroundAntibody-mediated rejection (AMR) is a major cause of allograft loss in kidney transplant. Although donor-specific anti–human leukocyte antigen antibody (DSA) is a key cause of AMR, not all patients with DSA are diagnosed as having AMR and show poor allograft outcomes. This study aimed to evaluate clinical significance of C3d-binding activity in patients with DSA identified by single-antigen bead (SAB) assay.MethodsA total of 168 recipients screened for DSA from 2015 to 2018 were enrolled. Among them, 52 patients had DSA confirmed by SAB assay. Sera were tested using the C3d assay on Luminex platform. AMR was defined by kidney allograft biopsy results using Banff 2015 criteria.ResultsOf 52 patients, C3d-binding DSAs were detected in 22 patients (42.3%). Indication allograft biopsy was performed in 35 patients, with 31 (88.6%) diagnosed as having AMR. Patients with C3d-binding DSA had more class II SAB-DSA (73.3% vs 100%, P = .015) and showed significantly higher mean (SD) fluorescence intensity of class II SAB-DSA than the C3d-binding DSA(?) group (9606.7 [6096.6] vs 1921.0 [1483.8], P < .001). There was a positive correlation in the highest mean fluorescence intensity between class II SAB-DSA and class II C3d-binding DSA (r = 0.70, P < .001). Patients with C3d-binding DSA showed worse death-censored graft survival than those with non-C3d-binding DSA (P = .023).ConclusionsThis study showed that presence of C3d-binding DSA was significantly associated with allograft loss in SAB-DSA–positive patients. Further trials are warranted.     

Can Fetuin-A Deficiency Predict the Severity of COVID-19 Disease in Kidney Transplant Recipients?

BackgroundThis study aims to investigate whether fetuin A deficiency predicts the prognosis of COVID-19 disease in kidney transplant recipients (KTRs).MethodThe study was conducted on 35 hospitalized KTRs with COVID-19 pneumonia between November 2020 and June 2021. Serums were collected for fetuin-A measurement at admission and after six months of follow-up. The demographic and laboratory data of the patients were recorded and analyzed with the appropriate statistical method.ResultsA total of 35 KTRs, 23 of which (65.7%) were men, were included in the study. The mean age of the patients was 51.6 ± 14.0 years. Seventeen (48.6%) patients had severe disease criteria and required intensive care (ICU) support. Biopsy-proven acute rejection developed in 6 (17.1%) patients in the follow-up. At admission, the median fetuin-A value was 173.5 mcg/mL (143.5-199.25) in the moderate disease group and 126.0 mcg/mL (89.4-165.5) in the severe patient group (p = 0.005). While the Median fetuin-A value at the time of diagnosis was 173.5 mcg/mL (143.5-199.25), and in the 6th month was 208 mcg/mL [184-229] (p<0.001). By ROC analysis, the effect of serum fetuin-A level in predicting the severity of COVID-19 disease was significant (AUC: 0.771, p = 0.006, 95% CI: 0.615-0.927). When serum fetuin-A cut-off value was taken as 138 mcg/mL to determine disease severity, it was shown to have 83.3% sensitivity and 64.7% specificity.ConclusionsSerum fetuin-A level can predict disease severity in kidney transplant recipients in the presence of active COVID-19 disease.     

Spot Urine Protein Measurements: Are these Accurate in Kidney Transplant Recipients?

BACKGROUND: Proteinuria and albuminuria are important markers of allograft pathology and are associated with graft loss and cardiovascular disease. Traditionally, these have been quantified using a 24-hr urine collection, but spot urine measurements (albumin-creatinine and protein-creatinine ratios) have become popular because of convenience. Aside from tests of correlation, there has been little evaluation of these measurements in kidney transplantation. METHODS: To further assess the value of albumin-creatinine and protein-creatinine ratios, we measured protein-creatinine ratio and 24-hr urine protein excretion (n=192) and albumin-creatinine ratio and 24-hr urine albumin excretion (n=189) in stable renal transplant patients. Bias (measured minus estimated value), precision, and accuracy was calculated. RESULTS: For the protein-creatinine ratio, percent bias ranged from 12% to 21%, and the accuracy (within 30% of 24-hr collection) was only 47% to 56% depending on the degree of proteinuria. For the albumin-creatinine ratio, percent bias ranged from 9% to 21%, and the accuracy (within 30%) ranged from 38% to 80% depending on the degree of albuminuria. There was no statistical difference between accuracy of protein-creatinine and albumin-creatinine ratios. CONCLUSIONS: The ability of the albumin-creatinine and protein-creatinine ratios to accurately predict 24-hr albumin and protein excretion is modest. Given the similar accuracy of both measurements, either protein-creatinine ratio or albumin-creatinine ratio can be used for monitoring protein excretion. However, given the limitations of both the albumin-creatinine ratio and protein-creatinine ratio in this population, a 24-hr urine collection should be considered before making major clinical decisions (e.g., biopsy) based on the presence of proteinuria.     

Low Body Mass Index in Kidney Transplant Recipients: Risk or Advantage for Long-Term Graft Function?

OBJECTIVES: Nutritional status is known to be a marker of overall health status and a strong predictor of patient survival in several diseases. Whereas obesity is suspected to have a negative influence on general renal transplantation outcomes, the relationship between impaired nutritional status and long-term kidney graft survival is not yet clear. METHODS: We retrospectively analyzed graft survival with a follow-up time of 5 to 12.5 years among 224 kidney transplantations. A Cox proportional hazards model was applied to estimate risk factors for loss of graft function. RESULTS: The Cox model initially showed no significant influence of the body mass index (BMI) at 1 year after transplantation on the risk of transplant failure (relative risk 0.97 per BMI unit, P = .34). When the patients were divided into two groups according to BMI, a clear disadvantage was shown in terms of long-term graft survival for the groups with a low BMI. The risk of loss of transplant function increased by a factor of 1.85 (relative risk) if the BMI 1 year after kidney transplantation was less than 23 (P = .035). CONCLUSIONS: These findings suggested impaired long-term kidney graft survival among patients with reduced nutritional status. This result is assumed to reflect improved immune function due to reduced nutrient availability, thus leading to reinforcement of chronic rejection processes. This assumption is consistent with the already known immunomodulatory effect of caloric restriction to mitigate T-cell activation.     

Is There Any Association Between Triglyceride–Glucose Index and Graft Function in Kidney Transplant Recipients?

BackgroundAlthough previous studies have illustrated the relationship between chronic kidney disease, coronary artery disease, erectile dysfunction, and the triglyceride–glucose index (TyGi), the relationship between this index and postoperative graft function in patients undergoing renal transplantation has yet to be investigated. In the present study, we aimed to reveal the association between the TyGi and renal graft outcomes in patients who underwent renal transplantation.MethodsWe retrospectively collected data on living and cadaveric kidney donor recipients between May 2019 and April 2022. The recipients’ age, sex, body mass index, preoperative fasting glucose and triglyceride levels, TyGi, estimated glomerular filtration rate (eGFR), and serum creatinine measurement data were recorded. The patients were divided into 2 groups according to their GFR values (group 1: GFR <60 mL/min/1.73 m²; group 2: GFR ≥60 mL/min/1.73 m²). Follow-up serum creatinine–eGFR levels and TyGi measurements were compared between the recipients in group 1 and group 2.ResultsThe mean TyGi measurements of the recipients were 8.79 ± 0.64 in group 1 and 8.83 ± 0.72 in group 2. There was no statistically significant difference in terms of the TyGi measurements between the 2 groups (P >. 05). No statistically significant correlation was found between the recipients’ creatinine, eGFR, and TyGi at 1st, 6th, and 12th postoperative months (P > .05).ConclusionsWe believe that the relationship between the TyGi and renal graft function can be more clearly understood in prospective studies that include a higher number of patients and a longer follow-up period.     

Conversion to Everolimus in Kidney Transplant Recipients: To Believe or Not Believe?

IntroductionImmunosuppression with calcineurin inhibitors (CNI) in renal transplantation is associated with chronic graft dysfunction, increased cardiovascular risk, and malignancies. Everolimus (EVR) appears to permit a CNI-sparing regimen among stable kidney recipients.AimThe aim of this study was to analyze the efficacy and safety of conversion from CNI to EVR.Material and MethodsThis was a retrospective registry-based study of all kidney transplant recipients converted from CNI to EVR between 2006 and 2010. One hundred fifty-one patients, including 69.5% males and with an overall mean age of 50.2 ± 12.7 years, underwent conversion to EVR at 37.0 ± 49.8 (16) months after transplantation with 33.7% during the first 6 months. Reasons for conversion included: CNI nephrotoxicity prevention (54.3%), chronic graft dysfunction (25.8%), malignant tumors (10.6%), CNI-adverse reactions (6.6%), and biopsy-proven CNI nephrotoxicity (2.6%). During a follow-up of 17.9 ± 9.9 months (range, 6–58.5), 18 patients (11.9%) were reconverted to CNI, 2 died with functioning grafts, and 2 lost kidney function.ResultsWe observed a significant (P < .001) increase in estimated glomerular filtration rate–Modification of Diet in Renal Disease (eGFR-MDRD) by 11.3% within 6 months: 56.7 ± 22.1 to 64.1 ± 23.4 mL/min/1.73 m². At final evaluation it was 13.7%, namely, to 65.5 ± 23.0 mL/min/1.73 m². At the end of follow-up the proportion of patients with >300 mg/d proteinuria increased from 7.9% to 23.3% (P = .001). Dyslipidemia prevalence increased from 69.5% to 77.5% (P = not significant [NS]) and arterial hypertension increased from 49% to 65.9% (P < .001) at the end of follow-up. Other reported side effects included oral ulcers (2.6%), edema (5.3%), interstitial pneumonitis (1.3%), and toxic hepatitis (1.3%), some of them leading to EVR discontinuation.ConclusionIn our population, renal function improved significantly after conversion from CNI to EVR. Although side effects were common, most were mild, withdrawal of EVR was necessary in a low percentage of cases. EVR appears to be an effective, safe alternative to CNI for maintenance therapy in selected kidney transplant recipients.     

Is Serum Magnesium Level Associated With Serum Lipid Levels in Kidney Transplant Recipients?

BackgroundMagnesium (Mg) is key in diabetes mellitus, hyperlipidemia, and cardiovascular disease.MethodsThis is a retrospective cross-sectional study including 103 kidney transplant recipients. Patients aged under 18 years, patients treated with Mg supplementation, antihyperlipidemic agents, or diuretics, and patients with active infection or malignancy were not enrolled. Patients were divided into 2 groups according to median serum Mg level. The atherogenic index of plasma was calculated by a logarithmic transformation of the number acquired by dividing the molar concentrations of serum triglyceride by high-density lipoprotein value.ResultsThe mean serum Mg level was 1.91 ± 0.28 mg/dL. Six patients (5.8%) had hypomagnesemia (Mg <1.5 mg/dL), and 2 (1.9%) had hypermagnesemia (Mg >2.6 mg/dL). Serum Mg level was negatively correlated with body mass index, estimated glomerular filtration rate (eGFR), and tacrolimus trough level and positively correlated with levels of phosphorus, total cholesterol, and low-density lipoprotein (LDL-C). There was no correlation between serum Mg and triglyceride, high-density lipoprotein, atherogenic index of plasma, and cyclosporin A trough level. Patients with Mg >1.87 mg/dL had lower eGFR, tacrolimus, and cyclosporin A trough level and higher total cholesterol and LDL-C compared to those with Mg ≤1.87 mg/dL. In adjusted ordinal analysis, eGFR (hazard ratio (HR): 0.981, 95% CI 0.964-0.999, P = .036) and total cholesterol (HR: 1.015, 95% CI 1.004-1.027, P = .008) were independently associated with serum Mg. In multivariate linear regression analysis, serum Mg level was independently associated with LDL-C (β = .296, t = 3.079, P = .003) and total cholesterol (β = .295, t = 3.075, P = .003).ConclusionSerum Mg level may have an important impact on dyslipidemia in kidney transplant recipients.