Prospective Study on Individualized Dose Adjustment of Tolvaptan Based on Urinary Osmolality in Patients With ADPKD.

Introduction: Tolvaptan has been shown to reduce renal volume and delay disease progression in autosomal-dominant polycystic kidney disease (ADPKD). However, no biomarkers are currently available to guide dose adjustment. We aimed to explore the possibility of individualized tolvaptan dose adjustments based on cut-off values for urinary osmolality (OsmU). Methods: This prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate [eGFR] during treatment), within-patient eGFR slope, and side effects were monitored during the 3-year follow-up. Results: Forty patients participated in the study. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose (mean dose, 64 [±10] mg), with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (±2.41) ml/min per 1.73 m2 during tolvaptan treatment, compared to the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients (mean time to onset, 31 months; 95% confidence interval [CI] = 28-34). Conclusion: Individualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.

Prognosis Factors of Patients Undergoing Renal Replacement Therapy.

BACKGROUND: Survival in patients with end-stage kidney disease (ESKD) on renal replacement therapy (RRT) is less than that of the general population of the same age, and depends on patient factors, the medical care received, and the type of RRT used. The objective of this study is to analyze the factors associated with survival in patients undergoing RRT. METHODS: We conducted a retrospective observational study of adult patients with an incident of ESKD on RRT in Andalusia from 1 January 2008 to 31 December 2018. Patient characteristics, nephrological care received, and survival from the beginning of RRT were evaluated. A survival model for the patient was developed according to the variables studied. RESULTS: A total of 11,551 patients were included. Median survival was 6.8 years (95% CI (6.6; 7.0)). After starting RRT, survival at one year and five years was 88.7% (95% CI (88.1; 89.3)) and 59.4% (95% CI (58.4; 60.4)), respectively. Age, initial comorbidity, diabetic nephropathy, and a venous catheter were independent risk factors. However, non-urgent initiation of RRT and follow-up in consultations for more than six months had a protective effect. It was identified that renal transplantation (RT) was the most influential independent factor in patient survival, with a risk ratio of 0.13 (95% CI (0.11; 0.14)). CONCLUSIONS: The receiving of a kidney transplant was the most beneficial modifiable factor in the survival of incident patients on RRT. We consider that the mortality of the renal replacement treatment should be adjusted, taking into account both modifiable and nonmodifiable factors to achieve a more precise and comparable interpretation.

Years of Potential Life Lost on Renal Replacement Therapy: Retrospective Study Cohort.

BACKGROUND: Chronic kidney disease is the non-communicable disease with the highest growth in morbidity and mortality. Renal transplantation (RT) is the first option of renal replacement in end-stage kidney disease (ESKD) and dialysis is an alternative. However, there is no objective quantification of the impact of both options on a patient's overall survival. The purpose of our study is to assess the potential years of life lost by patients on renal replacement therapy. METHODS: Retrospective study cohort conducted from 2008 to 2018 based on autonomic data registry. RESULTS: 11,551 patients included who received renal replacement therapy (RRT) in a range of age from 15 to 94 years. The mean age at the time of onset was 62.7 years, 95% confidence interval (95% CI) (62.4; 63.0). The mortality rate of RRT patients was 42.2%, 95% CI (41.5; 43.3) and the mean age at death was 72.7 years, 95% CI (72.4; 73.1). The number of patients with ESKD treated with RT was 3776, 32.7% of the total, 95% CI (31.8; 33.5). The total amount of years of potential life lost (YPLL) in the entire cohort was 77,831.3 years, 48,010.1 years in men, and 29,821.2 years in women. The mean number of YPLL per patient with RRT was 6.74 years in both sexes, 6.95 years in women, and 6.61 years in men. The mean number of potential years of life lost in dialysis patients was 9.0 years in both sexes, 8.8 years in men, and 9.2 years in women, while among kidney transplant recipients this figure decreased to 2.2 years in both men and women. CONCLUSIONS: End-stage chronic kidney disease in renal replacement therapy by dialysis causes an average of 9.0 years of life potentially lost for each patient on dialysis treatment, while having received a kidney transplant reduces this figure by 75.6%.

Neuroendocrine Gastroenteropancreatic Tumors: Where Are We?

AIMS: Neuroendocrine gastroenteropancreatic tumors are infrequently found neoplasms. Our objective was to analyze the survival rates for all sites that they occur in by studying different variables. MATERIALS AND METHODS: A retrospective study was carried out using records for a 7-year period from January 1, 2008 to December 31, 2014 on neuroendocrine gastroenteropancreatic tumors patients diagnosed at the Pontevedra-Salnés Hospital Complex. The variables used were as follows: age at diagnosis, tumor size, presence or absence of metastases at diagnosis, cell proliferation index, Ki-67 of each tumor, treatments received, postdiagnosis survival time, existence or not of tumor progression, and time from diagnosis to progression and from diagnosis to mortality. In relation to treatments, the information recorded was whether the treatment was endoscopic, surgical, or pharmacological. RESULTS: Ninety-three neuroendocrine tumors made up a ratio of 4.42 cases per 100,000 inhabitants per annum. The median patient follow-up time was 44 months. The overall 5-year survival rate for patients who were followed up for a minimum of 60 months (49 patients) was 65.3%. The progression-free survival was 75.6% for 41 patients who were followed up for a minimum of 60 months. The survival rate for patients receiving endoscopic treatment was 100%, as there was no patient mortality recorded for those treated by endoscopic resection during the follow-up period. CONCLUSION: Pancreatic neuroendocrine tumors may be managed conservatively in elderly patients by either monitoring them with imaging studies or treating them with somatostatin analogs. In the case of digestive tract tumors (stomach, duodenum, and rectum) that meet the criteria for endoscopic resection, this is a reliable and safe technique in the long term.

Coincidence of GIST and pancreatic endocrine neoplasm in neurofibromatosis.

Carcinoids of the ampulla of Vater are infrequent tumors of which a quarter of cases have been detected in patients with type I neurofibromatosis. This hereditary disease is also associated with gastrointestinal stromal tumors (GIST). However, the coincidence of these three entities together have only been formerly detected in five cases. A 53 year-old female patient, diagnosed with type I neurofibromatosis, with a malignant carcinoid of ampulla of Vater and multiple gastrointestinal stromal tumors in the duodenum and jejunum, was treated with total pancreatectomy and the excision of her intestinal tumors. Five-years on, a follow-up showed the patient to be well, and free from tumor recurrence. The coexistence of an ampullary carcinoid tumor, GIST and neurofibramatosis is very rare. Radical curative surgical resection is a good treatment option, but the optimal management of this is not yet well established.

Effect of imiquimod on partial-thickness burns.

BACKGROUND: Burns can result in substantial morbidity through fibroblast proliferation and contracture. Imiquimod (IMQ), an immune response modifier and upregulator of endogenous cytokine expression, has been shown to suppress fibroblast proliferation. It is widely used in the treatment of viral, neoplastic and non-neoplastic skin conditions and has recently been tested in the reduction of hypertrophic scarring and keloids. To our knowledge, no other study has so far evaluated the effect of IMQ on cutaneous burns. METHODS: Partial-thickness burns were produced on the dorsum of 32 Wistar rats. Right-sided wounds received saline and left-sided wounds received 5% IMQ cream three times/week following injury. Photographs taken on post-burn days (PBD) 4, 7, 14 and 21 were evaluated for wound appearance using a clinical assessment scale and a visual analog scale. Scars were measured by digital planimetry. Samples stained with hematoxylin-eosin were submitted to conventional histological analysis. Samples stained with Sirius Red were analyzed under polarized light for collagen morphometry. RESULTS: Visual scores were higher in the saline group on PBD 21 (p<0.05). Wound edge migration rates were lower (p<0.05) and conventional histology showed accentuated inflammation and delayed reepithelialization in the IMQ group. Type-I and type-III collagen deposition increased in the saline group and decreased in the IMQ group. Conversely, the proportion between type-I and type-III collagen differed significantly between treatments on PBD 4 and 21 (p<0.05 in both cases). CONCLUSIONS: Short-term topical imiquimod treatment of partial-thickness burns in rats did not improve clinical appearance and scarring but rather decreased fibrosis. Significant differences in collagen deposition were observed between the treatments.

Medical management of pneumonia caused by Rhodococcus equi in a renal transplant recipient.

Rhodococcus equi is an animal pathogen that occasionally causes opportunistic infections in immunocompromised patients. The most common clinical picture is one of necrotizing pneumonia with a tendency toward cavitation and the formation of abscesses. We report a case of pneumonia caused by R equi in a renal transplant patient. An excellent response was shown to antibiotic treatment. Symptoms regressed, and the progressive disappearance of the lesion was confirmed on follow-up computed tomography scans. Surgical intervention or other invasive procedures were not required. To our knowledge, 14 cases of infection by R equi in solid-organ transplant patients have been described to date. Nine were recipients of a renal allograft. Surgery was required in many of these patients, and all the renal transplant recipients required the use of invasive therapeutic techniques, such as pleural drainage. This is the first case of a renal transplant recipient in whom radiologic presentation was as a solid nodule without ensuing cavitation that resolved exclusively with antibiotic treatment.