The natural history of autosomal dominant polycystic kidney disease. A strategy for grouping families and mutations.

Autosomal dominant polycystic kidney disease (ADPKD) is a main cause of end-stage renal disease. Today, knowledge of its genetic basis has made it possible to develop strategies that prevent the transmission of the disease. OBJECTIVES: The objective of the study was to analyze the natural history of ADPKD in the province of Córdoba and to design a database that allows grouping families with different mutations. PATIENTS AND METHODS: All patients (n = 678) diagnosed with ADPKD followed by the Córdoba nephrology service are included. Various clinical variables (age and sex), genetic variables (mutation in PKD1, PKD2) and the need for renal replacement therapy (RRT) were retrospectively analyzed. RESULTS: The prevalence was 61 cases per 100,000 inhabitants. Median renal survival was significantly worse in PKD1 (57.5 years) than in PKD2 (70 years) (log-rank p = 0.000). We have genetically identified 43.8% of the population, detecting PKD1 mutations in 61.2% and PKD2 mutations in 37.4% of cases, respectively. The most frequent mutation, in PKD2 (c.2159del), appeared in 68 patients belonging to 10 different families. The one with the worst renal prognosis was a truncating mutation in PKD1 (c.9893 G > A). These patients required RRT at a median age of 38.7 years. CONCLUSIONS: Renal survival of ADPKD in the province of Córdoba is similar to that described in the literature. We detected PKD2 mutations in 37.4% of cases. This strategy allows us to know the genetic basis of a large proportion of our population while saving resources. This is essential to be able to offer primary prevention of ADPKD through preimplantation genetic diagnosis.

Long-term Kidney Function Evolution in Living Kidney Donors: A Single Center Experience.

Living donor kidney transplant is the best treatment for end-stage kidney disease, posing minimal perioperative morbimortality for the donor, although long-term consequences are subject of debate if donor acceptance widens. We present a retrospective observational study analyzing clinical, demographic, and analytical variables throughout the follow-up period of 60 kidney donors whose procedures were performed between 1985 and 2021 at our hospital. Donors were divided according to their previous high blood pressure status, analyzing kidney function and other clinical parameters throughout follow-up. There were no statistically significant differences, although there was a trend toward a higher uric acid levels and lower high-density lipoprotein cholesterol in predonation patients with hypertension, not yielding an excess of end-stage kidney disease between groups at the end of the follow-up. We also analyzed the evolution of estimated glomerular filtration rate (eGFR), dividing patients into tertiles, which resulted in none of the parameters associating a higher rate of progression. All donors had an eGFR >71 mL/min/1.73 m2 at the time of donation. Over time, a decline in eGFR <60 mL/min/m/1.73 m2 was observed in 26 patients (53.6%), measured by Chronic Kidney Disease Epidemiology Collaboration estimation and in 55.4% of the total (31 patients) by Modification of Diet in Renal Disease. At our center, kidney donors with adequate predonation eGFR, although presenting a reduction in postnephrectomy eGFR, remain stable afterward, with none of them reaching an eGFR <30 mL/min/1.73 m2. We found no differences in the impact of high blood pressure on long-term eGFR, nor predictive factors influencing the rate of eGFR decline. Studies with larger number of patients are needed to confirm these results.

Mesenchymal Stem Cells Current Clinical Applications: A Systematic Review.

INTRODUCTION: Human Mesenchymal Stem Cells (hMSCs) are multipotent stem cells capable of renewing themselves and differentiation in vitro into different kinds of tissues. In vivo hMSCs are sources of trophic factors modulating the immune system and inducing intrinsic stem cells to repair damaged tissues. Currently, there are multiple clinical trials (CT) using hMSCs for therapeutic purposes in a large number of clinical settings. MATERIAL AND METHODS: The search strategy on clinicaltrials.gov has focused on the key term "Mesenchymal Stem Cells", and the inclusion and exclusion criteria were separated into two stages. Stage 1, CT on phases 1-4: location, the field of application, phase, and status. For stage 2, CT that have published outcome results: field of application, treatment, intervention model, source, preparation methods, and results. RESULTS: By July 2020, there were a total of 1,138 registered CT. Most studies belong to either phase 2 (61.0%) or phase 1 (30.8%); most of them focused in the fields of traumatology, neurology, cardiology, and immunology. Only 18 clinical trials had published results: the most common source of isolation was bone marrow; the treatment varied from 1-200 M hMSCs; all of them have similar preparation methods; all of them have positive results with no serious adverse effects. CONCLUSIONS: There appears to be a broad potential for the clinical use of hMSCs with no reported serious adverse events. There are many trials in progress, their future results will help to explore the therapeutic potential of these promising cellular sources of medicinal signals.