Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability.

Foxp3(+) regulatory T cells (Treg cells) are required for immunological homeostasis. One notable distinction between conventional T cells (Tconv cells) and Treg cells is differences in the activity of phosphatidylinositol-3-OH kinase (PI(3)K); only Tconv cells downregulate PTEN, the main negative regulator of PI(3)K, upon activation. Here we found that control of PI(3)K in Treg cells was essential for lineage homeostasis and stability. Mice lacking Pten in Treg cells developed an autoimmune-lymphoproliferative disease characterized by excessive T helper type 1 (TH1) responses and B cell activation. Diminished control of PI(3)K activity in Treg cells led to reduced expression of the interleukin-2 (IL-2) receptor α subunit CD25, accumulation of Foxp3(+)CD25(-) cells and, ultimately, loss of expression of the transcription factor Foxp3 in these cells. Collectively, our data demonstrate that control of PI(3)K signaling by PTEN in Treg cells is critical for maintaining their homeostasis, function and stability.

Updated management for antibody-mediated rejection: opportunity to prolong kidney allograft survival.

PURPOSE OF REVIEW: Antibody-mediated rejection (ABMR) is an important barrier to achieve long-term kidney allograft survival. Human leukocyte antibody (HLA)-incompatibility and ABO-incompatibility are the two main mechanisms of ABMR. Nevertheless, the advances in managing ABMR have changed the paradigm for kidney transplantation. This review aimed to emphasize the HLA-incompatibility and ABO-incompatibility kidney transplant and update the management of ABMR. RECENT FINDINGS: HLA-incompatibility kidney transplantation is a strong risk factor for ABMR. Donor-specific antibody (DSA) is a surrogate biomarker that prevents long-term allograft survival. The standard treatment for ABMR has unfavorable results. New drugs that target the B cell are a promising approach to treat ABMR. In the past, ABO-incompatibility kidney donor was an absolute contraindication but now, it is widely accepted as an alternative organ resource. The advancement of ABO antibody removal and B-cell depletion therapy has been successfully developed. ABO isoagglutination remains the main biomarker for monitoring ABMR during the transplantation process. C4d staining without inflammation of the kidney allograft is the marker for the accommodation process. SUMMARY: With the shortage of organ donors, transplant experts have expanded the organ resources and learned how to overcome the immunological barriers by using novel biomarkers and developing new treatments that support long-term graft survival.

First Asian Kidney Donor Profile Index (KDPI) and Estimated Post-Transplant Survival (EPTS) models, with validation against US models in Thai population.

INTRODUCTION: Differences in transplant characteristics limit the application of kidney donor profile index (KDPI) and estimated post-transplant survival (EPTS) models developed in Western countries to Asian populations. METHODS: We analyzed data of the Thai Transplant Registry and the Thai Red Cross Society on 2558 DDKTs performed between 2001 and 2014. Thai KDPI and EPTS models were developed using Cox regression, and validation against the US models. RESULTS: Thai KDPI was developed based on seven donor factors: age, height, best estimated glomerular filtration rate, diabetes mellitus, hypertension, cerebrovascular accident, and adrenaline infusion. The Thai and US donor risk index had comparable predictive abilities for transplant survival (C-statistics .5871 vs. .5548; P = .429). KTs from donors with a US KDPI > 70% demonstrated significantly worse 5-year transplant survival. The Thai EPTS model was developed from four recipient factors: age, body weight, diabetes mellitus, and hepatitis C infection. The C-statistics of the Thai and US EPTS models were comparable (.5924 vs. .6039; P = .360). A US EPTS > 70% was revealed in only 2.5% of our cohort. CONCLUSIONS: The first simplified KDPI and EPTS models for an Asian population were developed. Our models are available at www.thai-kdpi-epts.org.

MicroRNA-21 in plasma exosome, but not from whole plasma, as a biomarker for the severe interstitial fibrosis and tubular atrophy (IF/TA) in post-renal transplantation.

BACKGROUND: Non-invasive diagnosis of interstitial fibrosis and tubular atrophy (IF/TA), a major cause of chronic allograft dysfunction in post-kidney transplantation (post-KT), is needed. OBJECTIVE: Several candidates of microRNAs (miRs) in plasma exosome or whole plasma were evaluated for IF/TA biomarker. METHODS: Kidney samples from biopsy and plasma were tested for miRs expression. RESULTS: Expression of miR-21, miR-142-3p and miR-221 in renal histology with high fibrosis score (Banff classification) was higher than the samples with lesser score (n = 17/group). However, expression of these miRs from plasma exosome or from whole plasma of post-KT patients with different severity of IF/TA as determined by percentage of IF/TA including; grade I (5-25%) (n = 15), grade II (26-50%) (n = 15), grade III (≥ 50%) (n = 6) versus stable graft function (no IF/TA) (n = 15) was not different. However, high expression of miR-21 in exosome, but not from whole plasma, was demonstrated in IF/TA grade II and III compared with IF/TA grade I. In contrast, serum creatinine (Scr) and proteinuria, the current standard biomarkers, could not differentiate IF/TA grade I out of grade II/III. There was no correlation between exosome miR-21 versus the current standard renal injury biomarkers, including Scr, blood urea nitrogen and proteinuria, in IF/TA grade II or grade III. CONCLUSIONS: High miR-21 in plasma exosome, but not in whole plasma, indicated high grade IF/TA in post-KT patients. This non-invasive monitoring biomarker allows the more frequent evaluation on IF/TA than renal biopsy (a standard but more invasive procedure) resulting in the earlier management. More studies on patients are warrant.

Risk factors and clinical outcomes of tuberculosis among kidney transplant recipients in high endemic country.

BACKGROUND: Tuberculosis (TB) is considered as a challenge issue in solid organ transplant recipients because of high morbidity and mortality. Active TB after transplant mostly occurs from reactivation of latent infection. Understanding risk factors and clinical information of TB may provide an appropriate prevention and treatment strategies in this specific patient population, however data from high endemic area is scarce. METHODS: A matched single-center, case-control study was conducted in our institute. Cases were defined as newly diagnosed confirmed or clinical active TB in patients who underwent kidney transplant (KT) between April 1992 and October 2018. For each case, 5 controls were matched by age and sex. Risk factor associated with TB was determined using univariate and multivariate conditional logistic regression. RESULTS: Between study period, KT was performed in 787 patients. Twenty-seven patients (3.43%) were diagnosed with active TB including 20 confirmed and 7 clinical diagnosed cases. The global incidence of TB in our population was 315 cases per 100 000 patients per year. Among 27 cases, pulmonary involvement was the most common (48.1%) followed by disseminated (18.5%), extrapulmonary (14.8%), pleura (11.1%) and pleuropulmonary (7.4%) TB. Allograft rejection was significantly associated with active TB (P < .001). The median onset duration of infection was 17 months (IQR, 4-59 months) after KT. Twenty-four (88.9%) patients received rifampicin containing regimen for treatment with median duration of 10 months (IQR, 6-12 months). All patients were cured after complete treatment, however those with TB remained having unfavorable outcomes including higher all-cause mortality and graft loss. CONCLUSIONS: Incidence rate of TB in KT recipients is higher than normal population. Allograft rejection was identified as a significant risk factor. Increase unfavorable outcomes including graft loss and mortality were also observed among patients with TB.

A case of successful treatment of severe COVID-19 pneumonia with favipiravir and tocilizumab in post-kidney transplant recipient.

We report a case of COVID-19 in kidney transplant patient in Thailand. A 58-year-old 2 years post-kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x-ray finding of bilateral multifocal patchy infiltration. COVID-19 infection has been confirmed by reverse real-time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High-flow nasal cannula oxygen therapy was required on days 4-5 of hospitalization. Tocilizumab was administered after rising of serum IL-6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti-viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.

Interference on Cytosolic DNA Activation Attenuates Sepsis Severity: Experiments on Cyclic GMP-AMP Synthase (cGAS) Deficient Mice.

Although the enhanced responses against serum cell-free DNA (cfDNA) in cases of sepsis-a life-threatening organ dysfunction due to systemic infection-are understood, the influence of the cytosolic DNA receptor cGAS (cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase) on sepsis is still unclear. Here, experiments on cGAS deficient (cGAS-/-) mice were conducted using cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) injection sepsis models and macrophages. Severity of CLP in cGAS-/- mice was less severe than in wildtype (WT) mice, as indicated by mortality, serum LPS, cfDNA, leukopenia, cytokines (TNF-α, IL-6 and IL-10), organ histology (lung, liver and kidney) and spleen apoptosis. With the LPS injection model, serum cytokines in cGAS-/- mice were lower than in WT mice, despite the similar serum cfDNA level. Likewise, in LPS-activated WT macrophages, the expression of several mitochondria-associated genes (as revealed by RNA sequencing analysis) and a profound reduction in mitochondrial parameters, including maximal respiration (determined by extracellular flux analysis), DNA (mtDNA) and mitochondrial abundance (revealed by fluorescent staining), were demonstrated. These data implied the impact of cfDNA resulting from LPS-induced cell injury. In parallel, an additive effect of bacterial DNA on LPS, seen in comparison with LPS alone, was demonstrated in WT macrophages, but not in cGAS-/- cells, as indicated by supernatant cytokines (TNF-α and IL-6), M1 proinflammatory polarization (iNOS and IL-1ß), cGAS, IFN-γ and supernatant cyclic GMP-AMP (cGAMP). In conclusion, cGAS activation by cfDNA from hosts (especially mtDNA) and bacteria was found to induce an additive proinflammatory effect on LPS-activated macrophages which was perhaps responsible for the more pronounced sepsis hyperinflammation observed in WT mice compared with the cGAS-/- group.

Phase II, multi-center, open-label, single-arm clinical trial evaluating the efficacy and safety of Mycophenolate Mofetil in patients with high-grade locally advanced or metastatic osteosarcoma (ESMMO): rationale and design of the ESMMO trial.

BACKGROUND: Clinical outcomes of patients with osteosarcoma remain unsatisfactory, with little improvement in a 5-year overall survival over the past three decades. There is a substantial need for further research and development to identify and develop more efficacious agents/regimens in order to improve clinical outcomes of patients for whom the prognosis is unfavorable. Recently, mycophenolate mofetil, a prodrug of mycophenolic acid, has been found to have anticancer activity against osteosarcoma in both in vitro and animal experiments, so that further investigation in humans is warranted. METHODS: A total of 27 patients with high-grade locally advanced or metastatic osteosarcoma will be enrolled into this phase II, multi-center, open-label, single-arm, two-stage clinical trial. The main objectives of this study are to determine the efficacy and safety of mycophenolate mofetil in the patients. The primary endpoint is progression-free survival at 16 weeks; the secondary endpoints include progression-free survival, overall survival, overall response rate, safety parameters, pharmacokinetic parameters, biomarkers, pain score, and quality of life. Mycophenolate mofetil at the initial dose of 5 g/day or lower will be administered for 4 cycles (28 days/cycle) or until disease progression or unacceptable toxicity. The dose of mycophenolate mofetil may be reduced by 1-2 g/day or withheld for some Grade 3 or Grade 4 toxicities whenever clinically needed. The duration of study participation is approximately 4-5 months, with a minimum of 12 study visits. If mycophenolate mofetil proves beneficial to some patients, as evidenced by stable disease or partial response at 16 weeks, administration of mycophenolate mofetil will continue in the extension period. DISCUSSION: This trial is the first step in the translation of therapeutic potential of mycophenolate mofetil emerging from in vitro and animal studies into the clinical domain. It is designed to assess the efficacy and safety of mycophenolate mofetil in patients with high-grade locally advanced or metastatic osteosarcoma. The results will provide important information about whether or not mycophenolate mofetil is worth further development. TRIAL REGISTRATION: This trial was prospectively registered on Thai Clinical Trials Registry (registration number: TCTR20190701001). The posted information will be updated as needed to reflect protocol amendments and study progress.

Maximizing anti-HBs seroresponsiveness in kidney transplant waitlist patients: A tertiary-center perspective
.

BACKGROUND: Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. MATERIALS AND METHODS: Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. RESULTS: A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥ 10 IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. CONCLUSION: Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.

The Cytochrome P450 3A5 Non-Expressor Kidney Allograft as a Risk Factor for Calcineurin Inhibitor Nephrotoxicity.

BACKGROUND: Tacrolimus is mainly metabolized by cytochrome P450 3A5 (CYP3A5), which is expressed in the liver. However, CYP3A5 is also expressed in the kidney tissue and may contribute to local tacrolimus clearance in the kidney allograft. We aimed to evaluate the association between the allograft CYP3A5 genotype and transplant outcomes. METHODS: We conducted a retrospective cohort study at the King Chulalongkorn Memorial Hospital, Thailand, comparing 2 groups of donor and recipient CYP3A5 genotypes, the expressor (*1/*1 and *1/*3) and the non-expressor (*3/*3). The primary outcomes were allograft complications including calcineurin inhibitor (CNI) nephrotoxicity and acute rejection episode. RESULTS: Of the 50 enrolled patients, 21 donors were expressors and 29 donors were the non-expressors. Tacrolimus trough concentrations were similar between the 2 genotypes. The incidence of CNI nephrotoxicity was higher in recipients with non-expressor donor genotype compared with the expressor donor genotype (72.4 vs. 33.3%, p = 0.006). CNI nephrotoxicity incidence was not different when recipient's genotypes were compared. Multivariate analysis from Cox-regression showed a hazard ratio of 3.18 (p = 0.026) for CNI nephrotoxicity in the non-expressor compared with the expressor donor. The recipient CYP3A5 genotypes did not significantly contribute to CNI nephrotoxicity. Kaplan-Meier analysis demonstrated the lowest CNI nephrotoxicity-free survival in recipients with the expressor genotype who received allograft from the non-expressor donors (p = 0.005). CONCLUSION: In conclusion, our results suggest that donor CYP3A5 non-expressor genotype (*3/*3) is a risk for CNI nephrotoxicity.

B-cell activating factor, a predictor of antibody mediated rejection in kidney transplantation recipients.

AIM: Donor-specific antibody (DSA) is a widely-used biomarker for antibody-mediated rejection (ABMR) but correctly indicates only 30-40% of patients with ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed. METHODS: All 68 kidney transplanted-recipients enrolled in this study were negative for graft rejection as determined by surveillance-biopsy ELISA at day 7 post-transplantation. Allograft biopsy was then performed at 6 months post-transplantation for subclinical-ABMR detection. Recipients were stratified by pre-transplant DSA and BAFF at day 7 into four groups. RESULTS: During the study period, 13.2% of the recipients demonstrated subclinical-ABMR at 6 months, without patient with clinical ABMR presentations. Overall mean BAFF at day 7 was 393 pg/mL (95% CI = 316-471 pg/mL). The optimal cut-off value for low vs. high BAFF level was 573 pg/mL, with sensitivity and specificity at 77.8% and 88.1%, respectively. Fifty percent of recipients with high BAFF at day 7 (14 patients) and only 3.7% of patients with low BAFF demonstrated ABMR (P < 0.05). Indeed, ABMR was more common in patients high BAFF level (hazard ratio = 7.30; 95% CI = 3.77-14.15). The prevalence of ABMR among negative pre-transplant DSA/low BAFF, positive DSA/low BAFF, negative DSA/high BAFF, and positive DSA/ high BAFF recipients were 4.4, 0, 37.5 and 66.7%, respectively (P < 0.05). CONCLUSIONS: Post-transplant ABMR can be predicted by perioperative serum BAFF level. Together with DSA testing, BAFF provides additional predictive value for ABMR.

Immunogenicity and safety of quadrivalent human papillomavirus types 6/11/16/18 recombinant vaccine in chronic kidney disease stage IV, V and VD.

Background: Up to >80% of sexually active adults will become infected with human papillomavirus (HPV) during their lifetime. Persistent HPV infection can result in cervical, vulvovaginal, penile and anogenital cancer. Clinical studies have shown the efficacy of three doses of quadrivalent HPV-6/11/16/18 L1 virus-like particle (VLP) vaccination, at Day 0, Month 2 and Month 6, to lower the occurrence of HPV infection and its complications. However, immunogenicity and safety of the HPV vaccine have not been proven in the chronic kidney disease (CKD) population. Methods: Sixty CKD stage IV, V and VD patients were enrolled for quadrivalent HPV-6/11/16/18 vaccination. A dose of vaccine was given at Day 0, Month 2 and Month 6. Each dose contained 20 µg HPV-6 L1 VLP, 40 µg HPV-11 L1 VLP, 40 µg HPV-16 L1 VLP and 20 µg HPV-18 L1 VLP, along with 225 µg of amorphous aluminum hydroxyphosphate sulfate adjuvant. HPV type-specific antibody response to neutralizing epitopes on HPV-6/11/16/18 was performed by multiplexed, competitive Luminex® immunoassays (cLIA) at Day 0 and Month 7. Results: At Day 0, anti-HPV seropositivity was 0-6.6% depending on HPV genotype. Patients who received three doses of vaccine had 98.2, 100, 100 and 98.2% seropositivity for genotypes 6/11/16/18, respectively. The average cLIA at Month 7 for genotypes 6/11/16/18 were 928.4 ± 231.1, 1136.1 ± 264.6, 6951.0 ± 1872.3 and 2196.3 ± 761.2 milliMerck units (mMu)/mL, respectively. No serious vaccine-related adverse events were observed. Conclusions: Quadrivalent HPV vaccine has been well tolerated, is safe and provides excellent immunogenicity in late-stage CKD.

Rituximab for recurrent IgA nephropathy in kidney transplantation: A report of three cases and proposed mechanisms.

AIM: Recurrent IgA nephropathy (IgAN) is a common recurrent glomerular disease after kidney transplantation. Recurrent IgAN, in particular, with crescent formation or endocapillary proliferation might result in kidney allograft loss. However, the current treatment options of recurrent IgAN are conflicting. METHODS: We have reported three kidney-transplanted recipients with biopsy-proven recurrent IgAN treated with four consecutive months of rituximab at the dose of 375 mg/1.73m2 without corticosteroids. RESULTS: At median follow-up 20 months following rituximab administration, all three recipients demonstrated decrease in proteinuria severity, slow disease progression with a well-tolerated condition. This therapeutic effect is most probably mediated by the B cell depletion. CONCLUSION: Our three case reports suggest that the disease severity of recurrent IgAN with endocapillary proliferation regardless of crescent formation can be minimized by the four doses of monthly rituximab regimen.

Validation of a 2-Point Limited Sampling Strategy to Predict the Tacrolimus Area-Under-the-12-Hour-Curve in Kidney Transplant Recipients.

BACKGROUND: Limited sampling strategies (LSS) have been proposed for predicting total exposure of tacrolimus, a widely used immunosuppressant in transplantation. This study aims to validate the equation developed by Wong et al for estimation of the tacrolimus area-under-the-concentration-over-12-hour-curve (AUC0-12) and to assess the effects of hemoglobin and duration of tacrolimus therapy on predictive performance of the equation in adult kidney transplant recipients. METHODS: Seven time point blood concentration profiles were collected from 31 stable kidney transplant recipients who received oral tacrolimus twice daily. The chemiluminescent microparticle immunoassay method was used to determine the tacrolimus concentration. Measured AUC0-12 (AUCm) was calculated by the linear trapezoidal rule. Predicted AUC0-12 (AUCp) was calculated using the equation that used tacrolimus concentrations measured at 2 hours (C2) and 4 hours (C4) after dose: 16.2 + 2.4(C2) + 5.9(C4). Predictive performance of the equation was determined by calculating bias and precision. Agreement between AUCp and AUCm was assessed. The effects of hemoglobin and duration of tacrolimus therapy on bias and precision were also evaluated. RESULTS: The median (interquartile range) of AUCm was 133.00 (98.25, 185.70) ng·h·mL. The AUCp well correlated with the AUCm (r = 0.962, P < 0.001). The equation had a mean percentage prediction error of -2.22% (95% CI, -5.14 to 0.71), mean absolute percentage prediction error of 6.67% (95% CI, 4.92-8.42), and root mean squared error (%CV) of 14.08 (10.29%) ng·h·mL. A Bland-Altman plot showed good agreement between AUCp and AUCm with a mean bias of -5.43 ng·h·mL (95% CI, -10.28 to -0.59). The hemoglobin level and duration of tacrolimus therapy did not influence the predictive performance of the equation. CONCLUSIONS: The equation had low bias and high precision in predicting the AUC0-12 of tacrolimus. The equation is a simple and reliable tool for estimating tacrolimus exposure.

Ear length and kidney function decline after kidney donation.

The preservation of kidney function after kidney donation depends on the kidney reserve - the potential of the remaining kidney to boost their function after loss of the other kidney. In Traditional Chinese Medicine, size and shape of the external ears are examined to evaluate the person's kidney health. We hypothesized that ear size might be a practical yet overlooked marker of kidney reserve. Fifty kidney transplantation donors were participated in this study. The length and width of both ears of all participants were measured during one of the post-donation visits. Pre-donation serum creatinine and post-donation serum creatinine as well as other relevant parameters (age, sex, weight, height, etc.) of the participants were extracted from medical records. The estimated GFR was calculated from serum creatinine, age and sex using the CKD-EPI equation. Ear length negatively associated with %GFR decline after kidney donation. For every 1 cm increase in ear length, it was associated with 5.7% less GFR decline after kidney donation (95% Confidence Interval 0.2 to 11.3, P = 0.04). Ear width, as well as age, sex, body weight, height, body mass index, and pre-donation eGFR did not significantly associate with the GFR decline. Our findings support the notion of Traditional Chinese Medicine that ear morphology may be associated with kidney health and suggest that ear length might be a useful predictor of kidney function decline after kidney donation.

Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue.

The prognosis of severe lupus nephritis (LN) is very different among individual patients. None of the current biomarkers can be used to predict the development of refractory LN. Because kidney histology is the gold standard for diagnosing LN, the authors hypothesize that molecular signatures detected in kidney biopsy tissue may have predictive value in determining the therapeutic response. Sixty-seven patients with biopsy-proven severely active LN by International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification III/IV were recruited. Twenty-three kidney tissue samples were used for RNA microarray analysis, while the remaining 44 samples were used for validation by real-time polymerase chain reaction (PCR) gene expression analysis. From hundreds of differential gene expressions in refractory LN, 12 candidates were selected for validation based on gene expression levels as well as relevant functions. The candidate biomarkers were members of the innate immune response molecules, adhesion molecules, calcium-binding receptors, and paracellular tight junction proteins. S100A8, ANXA13, CLDN19 and FAM46B were identified as the best kidney biomarkers for refractory LN, and COL8A1 was identified as the best marker for early loss of kidney function. These new molecular markers can be used to predict refractory LN and may eventually lead to novel molecular targets for therapy.

Acute tubular nephropathy in a patient with acute HIV infection: review of the literature.

We report a 57-year old man with diabetes mellitus and hypertension who presented with acute HIV infection. Routine blood tests showed an elevated blood urea nitrogen and creatinine. Renal biopsy showed acute tubular nephropathy, which has not been reported to occur during acute HIV infection, in the absence of rhabdomyolysis or multiple organ system failure. Antiretroviral therapy was initiated. His renal failure gradually resolved without further intervention. At one year of follow-up his HIV RNA was undetectable, and his renal function was normal. The case illustrates a rare manifestation of acute HIV infection - acute renal failure - in an older man with diabetes and hypertension. In this setting acute kidney injury might mistakenly have been attributed to his chronic comorbidities, and this case supports early HIV-1 testing in the setting of a high index of suspicion.