1. Investigación

Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage kidney disease worldwide. Its pathogenic mechanism is complex, and it can affect the entire structures of the kidneys such as the glomerulus, tubules and interstitium. Currently, the urinary albumin excretion rate and the estimated glomerular filtration rate are widely accepted as diagnostic criteria. However, some studies have reported a different or non-classical clinical course of DKD, with some patients showing declined kidney function with normal levels of albuminuria, known as the 'non-albuminuric DKD' phenotype. The pathogenesis of this phenotype remains unclear, but some clinical and pathological features have been postulated. This review explores the evidence regarding this topic.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with CKD. We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD. Methods: We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hr, eGFR 30-90 ml/min per 1.73 m2, who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline. Results: Of 57 patients screened, 46 were randomly assigned (mean eGFR, 58.1 ml/min per 1.73 m2; median UACR, 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was -19.6% (95% confidence interval [CI], -34.3 to -1.5), -33.7% (95% CI, -46.1 to -18.5), and -53% (95% CI, -61.7 to -42.4; P<0.001 versus dapagliflozin; P=0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone (r=-0.13; P=0.47; r=-0.08; P=0.66, respectively). Hyperkalemia was more frequently reported with eplerenone (n=8; 17.4%) compared with dapagliflozin (n=0; 0%) or dapagliflozin-eplerenone (n=2; 4.3%; P between-groups=0.003). Conclusions: Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment.

Connexins (Cx) are a family of transmembrane proteins that form gap junction intercellular channels that connect neighboring cells. These channels allow the passage of ions and other biomolecules smaller than 1 kDa, thereby synchronizing the cells both electrically and metabolically. Cxs are expressed in all retinal cell types and the diversity of Cx isoforms involved in the assembly of the channels provides a functional syncytium required for visual transduction. In this chapter, we summarize the status of current knowledge regarding Cx biology in retinal tissues and discuss how Cx dysfunction is associated with retinal disease pathophysiology. Although the contribution of Cx deficiency to retinal degeneration is not well understood, recent findings present Cx as a potential therapeutic target. Therefore, we will briefly discuss pharmacological approaches and gene therapies that are being explored to modulate Cx function and fight sight-threatening eye diseases.

BACKGROUND: There are still many barriers when implementing exercise routines within daily dialysis care, even though benefits are well-known. Developing cost-effective strategies is necessary to overcome these barriers and include exercise as a complementary therapy in dialysis. AIM: To compare several exercise programs on hemodialysis patient’s functional capacity and health-related quality of life. DESIGN: This study was a 16-week follow-up, two-parallel group trial with balanced randomization. SETTING: Participants in this study belonged to a private hospitalized care center. POPULATION: Referred sample of 71 patients that suffered end-stage chronic kidney disease who underwent hemodialysis for at least 3 months and had a medical stable condition. METHODS: Thirty-six participants performed for 16 weeks an intradialytic exercise program lead by the nursing staff of the hemodialysis unit and 35 a home-based program supervised by physical therapists of the hospital. RESULTS: The main researcher and the data analyst were both blinded to participant allocation. There was a significant effect in time for both groups. Participants improved significantly in the Short Performance Physical Battery (SPPB), One-Leg Heel-Rise (OLHR) and 6 Minute-Walk Test (6MWT), and in the Physical Activity Scale for the Elderly (PASE) and Short Survey Form 36 (SF-36) questionnaires. CONCLUSIONS: Nurse-led and home-based exercise interventions produce beneficial effects involving physical function, activity levels and health-related quality of life in patients undergoing hemodialysis. CLINICAL REHABILITATION IMPACT: The study emphasizes the importance of exercise rehabilitation routines in fragile populations such as dialysis patients, and the potential to overcome barriers for its daily implementation.

Background: Chronic kidney disease is closely related to a high risk of death and disability, poor physical performance and frailty. The main objective of this research was to analyse how intradialytic administration of a non-immersive virtual reality (VR) exercise programme would affect physical function and adherence to exercise in these patients. Methods: A total of 56 individuals participated in two 12-week periods in a crossover randomized controlled trial. Each patient underwent a functional capacity evaluation before and after each study period. The functional tests administered included the 4-m gait speed test, Short Physical Performance Battery (SPPB), timed up-and-go (TUG) test, one-legged stance test (OLST) for balance, sit-to-stand 10 (STS-10) and sit-to-stand 60 (STS-60) tests and 6-min walking test (6MWT). Adherence to the exercise programme was also recorded. To assess the effect of VR exercise on the functional test outcomes over time, the patients were analysed using a two-way repeated-measures analysis of variance with time and treatment as the within-participant factors. Results: By the end of the 12 weeks of exercise, compared with the control period, 33 participants showed significant change in physical function as measured through the 4-m gait speed test (0.14 m/s), SPPB (1.2 points), TUG (−1.7 s), OLST (7.1 s), STS-10 (−5.8 s), STS-60 (5 repetitions) and 6MWT (85.2 m), with adherence rates exceeding 70%. There were no changes in the biochemical data or in the medications in the period of the study. Conclusion: An intradialytic non-immersive VR exercise programme improves patient physical function.

Background: Intradialysis exercise programs in renal patients result in improved functional capacity, muscle strength, symptoms of depression, and health-related quality of life. Home-based exercise programs are an alternative to overcome logistical and human resource problems. However, the implementation of these programs is not an easy task and there is a lack of knowledge regarding the benefits associated with home-based exercise programs. Aim: To determine whether home-based exercise programs improve functional capacity, health-related quality of life, muscle strength, and symptoms of depression among patients with stage III–V chronic kidney disease. Methods: A systematic review and meta-analyses following PRISMA guidelines were utilized. Relevant articles were collected and independently assessed for their inclusion eligibility. Effects of home-based exercise were summarized by the standardized mean differences and represented by forest plots (Review Manager 5.4). Results: Eight studies were included, none of which reported any adverse effects. The intervention was usually aerobic, 76% of these programs lasted 3–6 months, and exercise adherence was 60–87.5%. Four studies measured health-related quality of life and found significant improvements in several subscales. Regarding functional capacity, five studies used the six-minute walking test (44.9 meters; 95% CI [30.45, 59.30]; p ≤ .001), three studies used the sit-to-stand-to-sit test (−0.45 seconds; 95% CI [−0.46, −0.26]; p ≤ .001), and two studies used the timed up-and-go test (−0.76 seconds; 95% CI [−1.38, −0.15]; p ≤ .001) and the handgrip strength test (1.16 kg; 95% CI [−2.88, 5.20]; p ≤ .001). LINKING EVIDENCE TO ACTION: Home-based exercise programs are beneficial to renal patients. These interventions are safe and effective to improve health-related quality of life and functional capacity and reduce symptoms of depression among patients with chronic kidney disease.

Progesterone (PG) has been shown to have a slowing effect on photoreceptor cell death in mouse models of retinitis pigmentosa when administered orally. The aim of this study was to investigate whether ophthalmically administered progesterone was able to reach neuroretina and thus, the distribution through ocular tissues of different PG formulations was studied. The effect of different initial PG concentration was also investigated. Different formulations with PG in their composition (drops, a corneal/scleral-insert and scleral-inserts) were prepared and assayed. Using whole porcine eyes, the different formulations were topically administered to the ocular surface. Frozen eyes were dissected, the PG in each tissue was extracted in acetonitrile and the amount of PG quantified by UHPLC-MS/MS. Our results show that after topical administration, PG diffuses from the ocular surface and distributes throughout all tissues of the eye. Lower levels of PG were found in sclera, choroid and neuroretina when PG was applied as drops compared to inserts. Our results also show that an increase in the initial PG concentrations applied, resulted in a statistically significant increase in the amounts of PG in aqueous humour, sclera, choroid and neuroretina.