Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney

Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan. Modeling shows that post-nephrectomy compensatory glomerular volume (GV) increase drives podocyte depletion and hypertrophic stress resulting in proteinuria and glomerulosclerosis, implying that GV increase could serve as a therapeutic target to prevent progression. In this report we examine how Angiotensin Converting Enzyme inhibition (ACEi), started before uninephrectomy can reduce compensatory GV increase in wild-type Fischer344 rats. An unbiased computer-assisted method was used for morphometric analysis. Urine Insulin-like growth factor-1 (IGF-1), the major diver of body and kidney growth, was used as a readout. In long-term (40-week) studies of uni-nephrectomized versus sham-nephrectomized rats a 2.2-fold increase in GV was associated with reduced podocyte density, increased proteinuria and glomerulosclerosis. Compensatory GV increase was largely prevented by ACEi started a week before but not after uni-nephrectomy with no measurable impact on long-term eGFR. Similarly, in short-term (14-day) studies, ACEi started a week before uni-nephrectomy reduced both GV increase and urine IGF-1 excretion. Thus, timing of ACEi in relation to uni-nephrectomy had significant impact on post-nephrectomy “compensatory” glomerular growth and outcomes that could potentially be used to improve kidney transplantation and live kidney donation outcomes.

Alport syndrome: our knowledge update

Alport syndrome is a progressive multisystem disease associated with variants in genes COL4A3, COL4A4, COL4A5.The syndrome is an important genetic cause of kidney failure, including women with X-linked disease. Given the unfavorable natural history of Alport nephropathy and benefit from early treatment with angiotensin-converting enzyme inhibition, it is necessary to change our diagnostic approach in patients with persistent glomerular hematuria and management of patients with Alport syndrome. This review presents the ethiology, pathogenesis, genotype and phenotype heterogeneity of the syndrome and expert clinical practice recommendations to enhancing early diagnosis and achieving optimal outcomes in Alport syndrome.

Angiotensin-converting enzyme inhibition: beyond blood pressure control – the role of zofenopril

The article highlights the main provisions of the review, which investigated the scope of clinical use of ACE inhibitors, in particular zofenopril, outside the control of blood pressure. Generalized clinical data are presented, indicating the benefits of its use in various diseases, in particular for the treatment of arterial hypertension, progression of chronic kidney disease, myocardial infarction, congestive heart failure and type 2 diabetes mellitus