Modes of action of lysophospholipids as endogenous activators of the TRPV4 ion channel.

The Transient Receptor Potential Vanilloid 4 (TRPV4) channel has been shown to function in many physiological and pathophysiological processes. Despite abundant information on its importance in physiology, very few endogenous agonists for this channel have been described, and very few underlying mechanisms for its activation have been clarified. TRPV4 is expressed by several types of cells, such as vascular endothelial, and skin and lung epithelial cells, where it plays pivotal roles in their function. In the present study, we show that TRPV4 is activated by lysophosphatidic acid (LPA) in both endogenous and heterologous expression systems, pinpointing this molecule as one of the few known endogenous agonists for TRPV4. Importantly, LPA is a bioactive glycerophospholipid, relevant in several physiological conditions, including inflammation and vascular function, where TRPV4 has also been found to be essential. Here we also provide mechanistic details of the activation of TRPV4 by LPA and another glycerophospholipid, lysophosphatidylcholine (LPC), and show that LPA directly interacts with both the N- and C-terminal regions of TRPV4 to activate this channel. Moreover, we show that LPC activates TRPV4 by producing an open state with a different single-channel conductance to that observed with LPA. Our data suggest that the activation of TRPV4 can be finely tuned in response to different endogenous lipids, highlighting this phenomenon as a regulator of cell and organismal physiology. KEY POINTS: The Transient Receptor Potential Vaniloid (TRPV) 4 ion channel is a widely distributed protein with important roles in normal and disease physiology for which few endogenous ligands are known. TRPV4 is activated by a bioactive lipid, lysophosphatidic acid (LPA) 18:1, in a dose-dependent manner, in both a primary and a heterologous expression system. Activation of TRPV4 by LPA18:1 requires residues in the N- and C-termini of the ion channel. Single-channel recordings show that TRPV4 is activated with a decreased current amplitude (conductance) in the presence of lysophosphatidylcholine (LPC) 18:1, while LPA18:1 and GSK101 activate the channel with a larger single-channel amplitude. Distinct single-channel amplitudes produced by LPA18:1 and LPC18:1 could differentially modulate the responses of the cells expressing TRPV4 under different physiological conditions.

Characteristics and outcomes of a Hispanic lupus nephritis cohort from Mexico.

OBJECTIVES: To characterize the clinical presentation and outcomes of LN in a Hispanic cohort from Mexico. METHODS: We studied 440 subjects with systemic lupus erythematosus and biopsy-proven LN followed for >36 months. We obtained demographic, clinical, laboratory, histopathological and treatment variables. All outcomes were analysed by survival analysis and included response to therapy, renal relapses, progression of kidney disease (decline in eGFR ≥ 30%, doubling of serum creatinine, end-stage kidney disease) and patient survival. RESULTS: The median age of the study cohort was 29 years (IQR 23-37) and 96% were female. The median eGFR at inclusion was 81 mL/min/1.73m2 (IQR 48-118) and 24 h-uPCR was 3.4 g/g (IQR 1.9-5.6). Mixed class LN (III/IV+V) was the most frequently observed (69%). Over a median follow-up of 79 months, complete response rates were 22.3%, 40.5% and 51.6%, at 6, 12 and 24 months, respectively. Renal relapse rates were 32.3% and 50.6% at 3 and 5 years. By 3 and 5 years, 20.7% and 31.4% had decline in eGFR ≥30%, 14.4% and 22.5% doubled their serum creatinine, and 9.1% and 17.7% progressed to ESKD. The factors associated with loss of kidney function were age, eGFR at presentation, the histologic chronicity index in the kidney biopsy, and the type of response to therapy. Patient survival was 98.2% and 97.1% at 3 and 5 years. CONCLUSION: Although the response to treatment and patient survival in this Latin American cohort is comparable to that observed in other regions, there is still a high rate of renal relapses and progression to decline in kidney function.

Effect of antimalarials on clinical outcomes in lupus nephritis.

OBJECTIVES: To evaluate the effect of antimalarial drugs in response to therapy, incidence of LN flares, and progression of kidney disease in a large LN cohort. METHODS: We retrospectively studied 424 biopsy-proven LN patients followed for >3 years. We obtained demographic, clinical, laboratory, histopathological, and treatment variables. Antimalarial use was approached as 1) users versus no users, 2) according to prevalent vs incident use regarding the LN flare, and 3) according to the type of antimalarial. All outcomes were evaluated by time-to-event analyses. Adjusted hazard ratios were obtained by Cox regression. RESULTS: The cohort included 424 patients, median age of 29 years (IQR 23-37), 96% female, with a median eGFR of 81 ml/min/1.73m2 (IQR 48-118) and proteinuria of 3.4 g/g (IQR 1.9-5.5). Antimalarial use was associated with higher complete response (aHR 1.57, 1.08-2.27), lower incidence of kidney flares (aHR 0.63, 0.43-0.92), and lower progression to kidney failure (aHR 0.37, 0.23-0.53). The effect on these outcomes was modified by the presentation eGFR, histological class, and/or concomitant initial immunosuppressor. These protective effects were observed in patients with prevalent or incident use regarding the LN flare and patients using hydroxychloroquine. The incidence of toxic retinopathy was 1.7%, 5.7%, and 8.8% by 3-, 5-, and 7 years of continued antimalarial use. CONCLUSION: The use of antimalarial drugs is associated with increased response to therapy, lower incidence of kidney flares, and lower progression to kidney failure in LN patients. Conversely, this population is at high risk of toxic maculopathy, and yearly ophthalmologic examination is recommended.

The influence of repeated flares in response to therapy and prognosis in lupus nephritis.

BACKGROUND: Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis. METHODS: All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival. RESULTS: A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups. CONCLUSIONS: A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.

Effect of Kidney transplantation on cyst growth in autosomal dominant polycystic kidney disease.

BACKGROUND: In patients with autosomal dominant polycystic kidney disease (ADPKD), there is limited evidence of the rate of cyst progression after kidney transplantation. AIMS: To compare the height-adjusted total kidney volume (Ht-TKV) before and after transplantation in kidney transplant recipients (KTR) with -ADPKD. MATERIALS AND METHODS: Retrospective cohort study. The estimate of Ht-TKV was calculated by the ellipsoid volume equation using measurements from CT or yearly MRI scans before and after transplantation. RESULTS: We included 30 patients with -ADPKD who underwent kidney transplantation (age 49 ± 10.1 years, 11 (37%) females, dialysis vintage 3 (1 - 6) years, and 4 (13%) underwent unilateral nephrectomy during the peritransplant period). The median follow-up time was 5 years (range 2 - 16 years). Transplantation was associated with a significant decrease in Ht-TKV after transplantation in 27 (90%) KTR. Median Ht-TKV decreased from 1,708 (IQR 1,100 - 2,350) mL/m to 710 (IQR 420 - 1,380) mL/m after 6 years of follow-up (p < 0.001), with a mean Ht-TKV change rate per year after transplantation of -1.4, -11.8, -9.7, -12.7, -7.0, and -9.4% after 1, 2, 3, 4, 5, and 6 years, respectively. Even in 2 (7%) KTR without regression, the annual growth was < 1.5% per year after transplantation. CONCLUSION: Kidney transplantation reduced Ht-TKV after the first 2 years of transplantation, and this decline was continuous for more than 6 years of follow-up.

Acute kidney injury in critically ill patients after oncological surgery: Risk factors and 1-year mortality.

AIM: We aimed to identify risk factors associated with acute kidney injury (AKI) and to analyse 1-year mortality after oncological surgery. METHODS: We retrospectively included 434 adult patients admitted to the intensive care unit (ICU) after oncological surgery, and classified AKI according to the Kidney Disease: Improving Global Outcomes criteria. We performed logistic regression and Cox regression analyses to evaluate AKI and mortality risk factors. RESULTS: Sixty-one percent of patients (n = 264) developed AKI. Previous abdominal radiotherapy and abdominal surgical packing were independently associated with stage 2 and 3 AKI, with adjusted odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.3-5.5, p = .010) and OR of 2.6 (95% CI 1.2-5.5, p = .014), respectively. Other independent risk factors were: glomerular filtration rate (eGFR) <60 ml/min/1.73m2 (OR 3.6, 95% CI 1.2-11.4, p = .028), abdominal surgery 2.6 (1.4-4.9, p = .003), intraoperative diuresis <1 ml/k/h (OR 2.4, 95% CI 1.4-4.0, p = .001), sepsis (OR 2.5, 95% CI 1.3-4.6, p = .002) and mechanical ventilation at ICU admission (OR 7.7, 95% CI 3.2-18.6, p < .001). Stage 2 and stage 3 AKI were independently associated with 1-year mortality, with adjusted hazard ratios (HR) of 2.6 (95% CI 1.3-5.0, p = .005) and HR of 5.0 (95% CI 2.6-9.6, p < .001), respectively. Additionally, patients who had postsurgical AKI, had a lower eGFR at 1-year follow-up. These findings may be limited by the retrospective single centre design of our study. CONCLUSION: In addition to the conventional risk factors, our results suggest that abdominal radiotherapy and abdominal surgical packing could be independent risk factors for AKI after oncological surgery.

Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus Nephritis.

BACKGROUND: Clinical distinction between patients with lupus nephritis who have active inflammation or chronic kidney damage is challenging. Studies have shown soluble CD163, which derives from cleavage of the CD163 M2c macrophage receptor and can be quantified in urine, correlates with active lupus nephritis. METHODS: We measured urine CD163 at lupus nephritis flares in patients from a Mexican cohort and cross-sectional and longitudinal United States cohorts. We also performed serial urine CD163 measurements during the treatment of flares in a subset of patients from the Mexican and longitudinal United States cohorts, and assessed response to therapy at 12 months. In addition, we evaluated urinary CD163 agreement with histologic activity in 19 patients from the Mexican cohort who had repeated kidney biopsies on follow-up. RESULTS: Urinary CD163 levels were significantly higher in patients with active lupus nephritis than in patients with active extrarenal SLE, inactive SLE, and other glomerular diseases, and correlated with disease clinical severity, histologic class, and the histologic activity index. Urinary CD163 increased from 6 months preflare to flare, diminishing progressively in complete and partial responders, whereas it remained elevated in nonresponders. Urinary CD163 <370 ng/mmol at 6 months predicted complete renal response at 12 months with >87% sensitivity and >87% specificity. Urinary CD163 <370 ng/mmol or >370 ng/mmol perfectly agreed (κ=1.0) with a histologic activity index ≤1 or >1 in repeated biopsies, respectively. Evaluation of urinary CD163 in patients with persistent proteinuria at 6 months improved the prediction of who would achieve complete renal response at 12 months. CONCLUSIONS: Urinary CD163 reflects histologic inflammation in lupus nephritis and is a promising activity biomarker that varies over time with lupus nephritis activity and treatment.

Perioperative fosfomycin disodium prophylaxis against urinary tract infection in renal transplant recipients: a randomized clinical trial.

BACKGROUND: Symptomatic urinary tract infection (UTI) is the most common infectious complication in renal transplant recipients (RTRs). Fosfomycin (FOS) is an attractive alternative for prophylaxis because it does not interact with immunosuppressants; although 90% is excreted unchanged in the urine, it does not require adjustment for renal function for single dose prophylaxis. METHODS: RTRs were recruited into this randomized, double-blind, placebo-controlled trial. Participants were randomized (1:1) to receive one 4 g dose of FOS disodium intravenously 3 h (FOS group) or placebo (placebo group) before placement and removal of a urinary catheter and before removal of a double-J ureteral stent. All participants received prophylaxis with trimethoprim/sulfamethoxazole. The main outcome was a comparison of the mean number of symptomatic UTI and asymptomatic bacteriuria (AB) episodes per patient during a 7-week follow-up period. The study was registered at ClinicalTrials.gov, NTC03235947. RESULTS: Eighty-two participants were included (41 in the FOS group and 41 in placebo group). The mean number of AB or symptomatic UTI episodes per patient was lower in the FOS group [intention-to-treat (ITT) 0.29 versus 0.60, P = 0.04]. The incidence of symptomatic UTI was lower in the FOS group (ITT, 7.3% versus 36.6%, P = 0.001), and there was no difference in the incidence of AB between both groups. The incidence of adverse events was similar in both groups. CONCLUSIONS: FOS addition is an effective and safe strategy to reduce the number of symptomatic UTIs during the first 7 weeks after renal transplant.

A Risk Score to Predict Admission to the Intensive Care Unit in Patients with COVID-19: the ABC-GOALS score.

OBJECTIVE: To develop a score to predict the need for ICU admission in COVID-19. METHODS: We assessed patients admitted to a COVID-19 center in Mexico. Patients were segregated into a group that required ICU admission, and a group that never required ICU admission. By logistic regression, we derived predictive models including clinical, laboratory, and imaging findings. The ABC-GOALS was constructed and compared to other scores. RESULTS: We included 329 and 240 patients in the development and validation cohorts, respectively. One-hundred-fifteen patients from each cohort required ICU admission. The clinical (ABC-GOALSc), clinical+laboratory (ABC-GOALScl), clinical+laboratory+image (ABC-GOALSclx) models area under the curve were 0.79 (95%CI=0.74-0.83) and 0.77 (95%CI=0.71-0.83), 0.86 (95%CI=0.82-0.90) and 0.87 (95%CI=0.83-0.92), 0.88 (95%CI=0.84-0.92) and 0.86 (95%CI=0.81-0.90), in the development and validation cohorts, respectively. The ABC-GOALScl and ABC-GOALSclx outperformed other COVID-19 and pneumonia predictive scores. CONCLUSION: ABC-GOALS is a tool to timely predict the need for admission to ICU in COVID-19.

LECT2 Amyloidosis in Kidney Transplantation: A Report of 5 Cases.

Leukocyte chemotactic factor 2 (LECT2) amyloidosis is a recently recognized entity that often affects the kidneys. Little information is available regarding kidney transplant outcomes in patients with LECT2 amyloidosis or who received kidney allografts containing LECT2 amyloid. We present clinical findings and allograft outcomes of 5 patients who received kidneys with donor-derived LECT2 amyloidosis. In all 5, LECT2 amyloidosis was discovered during protocol biopsies or in evaluation of suspected rejection. Less than 10% of kidney parenchyma was involved, with mostly interstitial and vascular deposits. Allograft function was not impaired and the amyloid deposits persisted for up to 8 years of follow-up. We conclude that kidneys with limited and localized LECT2 amyloid deposits that are otherwise suitable for transplantation need not be automatically discarded.

TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.

BACKGROUND: There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE: The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS: We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS: In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS: In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

Simple risk score for prediction of haemorrhagic complications after a percutaneous renal biopsy.

AIM: To derive a simple risk score to predict the individual risk of major complications for patients undergoing a percutaneous renal biopsy procedure of native kidneys. METHODS: The risk score was derived from a cohort of 1205 adult patients subjected to percutaneous renal biopsy and assigned to training and validation datasets. Factors associated with major complications were derived from univariate analysis and then modelled by stepwise multivariate logistic regression. Based on the odds ratio, independent predictors were assigned a weighted integer. The risk score is calculated from the sum of the integers. RESULTS: The overall incidence of major complications was 3.2%. Independent factors associated with MC were lower pre-biopsy haemoglobin, lower platelets, higher blood urea nitrogen, documented chronic kidney disease features in pre-biopsy ultrasound (US) and the presence of haematoma in the post-biopsy US. A score for pre-biopsy evaluation included the first four predictors and stratified patients in three categories with increasing risk at higher scores (low-risk 0.1%, moderate-risk 3.0% and high-risk 26.1%). The score demonstrated good discriminative power (AUC = 0.872). The addition of post-biopsy US findings increased the discriminative power (AUC = 0.938). A higher post-biopsy risk score was also associated with a higher incidence of MC (low-risk 0.2%, moderate-risk 2.7%, high-risk 16.9%). CONCLUSION: The risk of major complications after a percutaneous renal biopsy can be assessed by a simple risk score calculated from readily available information.

Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies.

BACKGROUND: Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS: The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS: The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS: The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.

Advances and challenges in renal transplantation in Latin America.

Latin America is a region made up of 33 countries that share many characteristics with each other. Since the first kidney transplant in Argentina in 1957, most of the Latin American countries have had a continuous increase in renal transplant activity, accounting for an increase in the total number of kidney transplants over time. In the last years, several advances have been made in the area of renal transplantation in Latin America: There are transplantation activities in almost all countries, the kidney transplantation rate from deceased donors has steadily increased, and almost all the countries have an appropriate legislation for transplantation activity. But much remains to be done to increase the kidney transplantation rate in order to cover the current demand. This could be achieved by ensuring unlimited access to renal transplantation, by improving deceased-donor programs to match the increasing burden of chronic diseases, and by incorporating new technology, new tools, and more trained people in transplant programs.

Increased phosphorylation of the renal Na+-Cl- cotransporter in male kidney transplant recipient patients with hypertension: a prospective cohort.

Evidence in rodents suggests that tacrolimus-induced posttransplant hypertension is due to upregulation of the thiazide-sensitive Na+-Cl- cotransporter NCC. Here, we analyzed whether a similar mechanism is involved in posttransplant hypertension in humans. From January 2013 to June 2014, all adult kidney transplant recipients receiving a kidney allograft were enrolled in a prospective cohort study. All patients received tacrolimus as part of the immunosuppressive therapy. Six months after surgery, we assessed general clinical and laboratory variables, tacrolimus trough blood levels, and ambulatory 24-h blood pressure monitoring. Urinary exosomes were extracted to perform Western blot analysis using total and phospho-NCC antibodies. A total of 52 patients, including 17 women and 35 men, were followed. At 6 mo after transplantation, of the 35 men, 17 developed hypertension and 18 remained normotensive, while high blood pressure was observed in only 3 of 17 women. The hypertensive patients were significantly older than the normotensive group; however, there were no significant differences in body weight, history of acute rejection, renal function, and tacrolimus trough levels. In urinary exosomes, hypertensive patients showed higher NCC expression (1.7±0.19) than normotensive (1±0.13) (P=0.0096). Also, NCC phosphorylation levels were significantly higher in the hypertensive patients (1.57±0.16 vs. 1±0.07; P=0.0049). Our data show that there is a positive correlation between NCC expression/phosphorylation in urinary exosomes and the development of hypertension in posttransplant male patients treated with tacrolimus. Our results are consistent with the hypothesis that NCC activation plays a major role in tacrolimus-induced hypertension.

Heat shock protein 72 (Hsp72) specific induction and temporal stability in urine samples as a reliable biomarker of acute kidney injury (AKI).

We demonstrated that urinary heat shock protein of 72 KDa (Hsp72) is a sensitive biomarker for the early detection of acute kidney injury (AKI). However, whether Hsp72 induction during an AKI episode is kidney-specific is unknown, as well as, the degree of Hsp72 stability in urine samples. In rats that underwent bilateral renal ischemia and reperfusion (I/R), Hsp72 levels were evaluated in several tissues and in collected urines under different storage and temperature conditions, as well as in variable numbers of freeze-thaw cycles. The effect of room temperature and five freeze-thaw cycles on urinary Hsp72 levels was also evaluated in urine samples from AKI patients. We found that Hsp72 increased exclusively in the renal cortex of I/R group, emphasizing its performance as an AKI biomarker. Urinary-Hsp72 remained constant at room temperature (48 h), during 9 months of storage and was not affected by five freeze/thaw cycles.

Urinary neutrophil gelatinase-associated lipocalin predicts graft loss after acute kidney injury in kidney transplant.

OBJECTIVE: Establish the prognostic value for graft loss of urinary neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (uKIM-1), interleukin-18 (uIL-18), and heat shock protein 72 (uHsp72) in kidney transplant recipients (KTR) with acute kidney injury (AKI). METHODS: Biomarkers were measured in 67 KTR with AKI caused by different entities. RESULTS: After 1 year, 11 KTR with graft loss had higher uNGAL compared to KTR without loss (p < 0.001). There were no differences for uKIM-1, uIL-18 and uHsp-72. uNGAL >200 ng/mL had 84% sensitivity and 86% specificity for graft loss (ROC AUC: 0.89, 95% CI: 0.81-0.97). uNGAL may be useful to predict graft loss after AKI.

Tubular urinary biomarkers do not identify aetiology of acute kidney injury in kidney transplant recipients.

AIM: To evaluate the performance of urinary neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule, interleukin-18 and heat shock protein 72 for differential diagnosis between causes of acute kidney injury in kidney transplant recipients, especially immunological rejection. PATIENTS AND METHODS: We measured these biomarkers in 67 kidney transplant recipients with acute kidney injury according to the RIFLE criteria. RESULTS: There were no statistical differences in biomarkers between kidney transplant recipients with immunological rejection (n = 20), pre-renal causes (n = 20) and other AKI causes (n = 27). Only the uNGAL level relative to urinary creatinine (uNGAL/uCr) for immunological rejection was different in comparison with others (P < 0.001); a cut-off of 59 µg/g of uNGAL/uCr had a sensitivity and specificity of 60% and 58% respectively (area under the curve in receiver-operating characteristic curve, 0.65). The other biomarkers were not useful in differentiating the causes of acute kidney injury. CONCLUSION: The biomarkers tested are not useful in identifying immunological rejection as cause of acute kidney injury in kidney transplant recipients.

Pre-transplant angiotensin II type 1receptor antibodies: a risk factor for decreased kidney graft function in the early post-transplant period?

Angiotensin II type 1 receptor antibodies (AT1Rab) are associated to a significantly lower graft survival and a higher risk of acute rejection after kidney transplantation. This study aimed to evaluate graft function and BPAR during the 1st year post-transplant (PT) in adult kidney transplant recipients (KTR), between 03/2009 and 08/2012. Pre-KT sera were screened for AT1Rab (ELISA) and HLA-DSA (Luminex). Three groups were analyzed: AT1Rab only (n = 13); HLA-DSA only (n = 8); and no AT1Rab or HLA-DSA (n = 90). No differences were observed in clinical characteristics across groups. A higher percentage of BPAR was observed in the AT1Rab positive group, but this difference was not significant. KTR with AT1Rab had a lower mean eGFR (20 mL/min/1.73m2) when compared to KTR with no Abs at 12 months. The significant difference in eGFR was observed since the 1st month PT. Multivariate analysis showed 4 factors independently and significantly associated with eGFR at 12mos PT: BPAR (-18.7 95%, CI -28.2 to -9.26, p<0.001), AT1Rab (-10.51, CI -20.9 to -0.095, p = 0.048), donor age (-0.42, CI -0.75 to -0.103 p = 0.010), and recipient age (-0.36, CI -0.67 to -0.048, p = 0.024). In this study AT1Rab in pre-transplant sera from KTR, was an independent and significant risk factor contributing to a lower eGFR 12 months. PT. This finding deserves to be confirmed in a larger KTR population.