Kidney transplantation (KTx) is the best therapeutic approach for chronic kidney diseases leading to irreversible kidney failure. Considering the origin of the graft, several studies have reported differences between living (LD) and deceased donors (DD) in graft and patient survival. These differences seem to be related to multiple factors including, donor age and time of cold ischemia among others. Many of transplanted organs come from old-aged DDs, in which pre-transplant biopsy is recommended. However, kidney biopsy has several limitations, and there is a need to develop alternatives to assess the status of a kidney before transplantation. As the analysis of urinary extracellular vesicles (uEVs) rendered promising results as non-invasive biomarkers of kidney-related pathologies, this pilot study aimed to investigate whether profiling uEVs of LDs and DDs may be of help to assess the quality of the kidney before nephrectomy. uEVs from 5 living donors and 7 deceased donors were isolated by size-exclusion chromatography, and their protein and miRNA content were analysed by liquid chromatography followed by mass spectrometry and next generation sequencing, respectively. Then, hierarchical clustering and venn diagrams were done with Perseus software and InteractiVenn tool. Specific EVs data bases were also used for Gene Ontology analysis. Next generation sequencing revealed that uEVs from DDs contained less miRNAs than LDs, but most of the DD-expressed miRNAs were shared with LDs (96%). Only miR-326 (targeting the apoptotic-related Bcl2) was found significantly over-represented in LD. Focusing on the protein content, we detected a low intra-group correlation in both types of donors. Despite these differences, hierarchical clustering of either miRNA or protein data could not identify a differential profile between LDs and DDs. Of note, 90% of transplanted patients had a functional graft after a year from KTx. In this pilot study we found that, in normo-functional grafts, minor differences in uEVs profile could not discriminate between LDs and DDs.

Use of immunosuppressive drugs is still unavoidable in kidney-transplanted patients. Since their discovery, calcineurin inhibitors (CNI) have been considered the first-line immunosuppressive agents, in spite of their known nephrotoxicity. Chronic CNI toxicity (CNIT) may lead to kidney fibrosis, a threatening scenario for graft survival. However, there is still controversy regarding CNIT diagnosis, monitoring and therapeutic management, and their specific effects at the molecular level are not fully known. Aiming to better characterize CNIT patients, in the present study, we collected urine from kidney-transplanted patients treated with CNI who (i) had a normal kidney function, (ii) suffered CNIT, or (iii) presented interstitial fibrosis and tubular atrophy (IFTA). Urinary extracellular vesicles (uEV) were enriched and the proteome was analyzed to get insight into changes happening during CNI. Members of the uroplakin and plakin families were significantly upregulated in the CNIT group, suggesting an important role in CNIT processes. Although biomarkers cannot be asserted from this single pilot study, our results evidence the potential of uEV as a source of non-invasive protein biomarkers for a better detection and monitoring of this renal alteration in kidney-transplanted patients.

Spain has dramatically increased the number of controlled circulatory death donors (cDCD). The initial selection criteria for considering cDCD for kidney transplantation (KT) have been expanded progressively, with practically no limits in donor age during the last years. We aimed to analyze the early clinical outcomes using expanded (> 65 years) cDCD in comparison with standard ones. Observational multicenter study including 19 transplant centers in Spain. We performed a systematic inclusion in a central database of every KT from expanded cDCD at each participant unit from January-2012 to January-2017. Surgical procedures and immunosuppressive protocols were based on local practices. Data was analyzed in the central office using logistic and Cox regression or competitive-risk models for multivariate analysis. Median time of follow-up was 18.1 months. 561 KT were performed with kidneys from cDCD, 135 from donors older than 65 years. As expected, recipients from older cDCD were also older (65.8 (SD 8.8) vs 53.7 (SD 11.4) years; p < 0.001) and with higher comorbidity. At 1 year, no differences were found amongst older and younger cDCD KT recipients in terms of serum creatinine (1.6 (SD 0.7) vs 1.5 (SD 0.8) mg/dl; p = 0.29). Non-death censored graft survival was inferior, but death-censored graft survival was not different (95.5 vs 98.2% respectively; p = 0.481). They also presented a trend towards higher delayed graft function (55.4 vs 46.7%; p = 0.09) but a similar rate of primary non-function (3.7 vs 3.1%; p = 0.71), and acute rejection (3.0 vs 6.3%; p = 0.135). In the multivariate analysis, in short follow-up, donor age was not related with worse survival or poor kidney function (eGFR < 30 ml/min). The use of kidneys from expanded cDCD is increasing for older and comorbid patients. Short-term graft outcomes are similar for expanded and standard cDCD, so they constitute a good-enough source of kidneys to improve the options of KT wait-listed patients.

Prevalence of kidney disease (KD) is increasing among human immunodeficiency virus (HIV)-infected population. Different factors have been related, varying on different published series. The objectives were to study prevalence of KD in those patients, its evolution, and associated risk factors. An observational cohort study of 1596 HIV-positive patients with cross-sectional data collection in 2008 and 2010 was conducted. We obtained clinical and laboratory markers, and registered previous or current treatment with tenofovir (TDF) and indinavir (IDV). The sample was divided according to estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) equation. Group 1: eGFR ≤60 mL/min/1.73 m2; group 2: eGFR >60 mL/min/1.73 m2. Among the patients, 76.4% were men, mean age (SD) 45 ± 9 years, time since diagnose of HIV 14 ± 7 years, and 47.2% of the patients received previous treatment with TDF and 39.1% with IDV. In 2008, eGFR ≤60: 4.9% (91.4% of them in chronic kidney disease [CKD] stage 3, eGFR 59–30 mL/min); this group was older, presented higher fibrinogen levels, and more patients were treated previously with TDF and IDV. In 2010, eGFR ≤60: 3.9% (87.1% stage 3 CKD). The 2.4% of cohort showed renal improvement and 1.3% decline of renal function over time. The absence of hypertension and treatment with TDF were associated with improvement in eGFR. Increased age, elevated fibrinogen, decreased albumin, diabetes mellitus, hyperTG, and worse virological control were risk factors for renal impairment. The HIV-positive patients in our area have a CKD prevalence of 4% to 5% (90% stage 3 CKD) associated with ageing, inflammation, worse immune control of HIV, TDF treatment, and metabolic syndrome.

Background: Kidney disease is an increasingly important comorbidity in people with HIV (PWH), owing to its association with mortality and cardiovascular (CV) disease, a leading cause of non-AIDS-related death. Sodium–glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have demonstrated renal and cardiovascular protective effects in the general population, but evidence in PWH remains scarce. We aimed to evaluate the safety and clinical effects of dapagliflozin in PWH with chronic kidney disease (CKD). Methods: We enrolled adult PWH with an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73 m² who were receiving stable antiretroviral therapy and had sustained HIV virological suppression. Participants received dapagliflozin 10 mg once daily according to routine clinical practice. Safety and efficacy outcomes, blood and urine biochemistry, 24-hour ambulatory blood pressure monitoring, adipose and muscle composition, and body water distribution were assessed. Analyses were performed in the overall cohort and stratified by gender and diabetes status. Results: Thirty-seven participants were included. Most were cisgender men (78%), and the median age was 60 years. One participant discontinued treatment because of dizziness. Renal parameters showed a consistent, although non-significant, trend toward improvement. Haematocrit and haemoglobin increased significantly in the overall cohort (both p < 0.001). HDL cholesterol increased significantly among participants with diabetes (p = 0.034). Body mass index (BMI) decreased from 26.48 kg/m² (IQR 24.00–29.38) to 26.22 kg/m² (IQR 23.58–28.42; p < 0.001), and waist circumference decreased from 102.3 cm (IQR 92.4–108.8) to 101.6 cm (IQR 90.85–107.55; p = 0.009). In men, rectus femoris cross-sectional area decreased significantly from 7.12 cm² to 6.65 cm² (p = 0.033), although no significant DXA-assessed changes in muscle composition were observed. All ultrasound-assessed abdominal fat layers decreased, but only omental fat thickness reached statistical significance, decreasing from 75.2 mm (IQR 39.6–81.9) to 58.6 mm (IQR 44.1–73.5; p = 0.029). The extracellular water-to-total body water ratio increased significantly in the overall cohort, from 0.378 (IQR 0.372–0.387) to 0.379 (IQR 0.372–0.387; p = 0.044), and among participants with diabetes, from 0.381 (IQR 0.375–0.388) to 0.383 (IQR 0.383–0.392; p = 0.014). Conclusions: In this cohort of PWH with CKD, dapagliflozin was well tolerated and associated with a trend toward improved renal function, together with significant reductions in BMI, waist circumference and omental fat thickness, a marker of cardiometabolic risk. Longer follow-up and larger studies are needed to confirm these benefits and determine their impact on cardiovascular outcomes.