Search

The development of complement inhibitors represented one of the major breakthroughs in clinical nephrology in the last decade. Complement inhibition has dramatically transformed the outcome of one of the most severe kidney diseases, the atypical hemolytic uremic syndrome (aHUS), a prototypic complement-mediated disorder. The availability of complement inhibitors has also opened new promising perspectives for the management of several other kidney diseases in which complement activation is involved to a variable extent. With the rapidly growing number of complement inhibitors tested in a rapidly increasing number of indications, a rational use of this innovative and expensive new therapeutic class has become crucial. The present review aims to summarize what we know, and what we still ignore, regarding complement activation and therapeutic inhibition in kidney diseases. It also provides some clues and elements of thoughts for a rational approach of complement modulation in kidney diseases.

Background and objectives C3 glomerulopathy and idiopathic immunoglobulin-associated membranoproliferative glomerulonephritis (Ig-MPGN) are kidney diseases characterised by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients reach end stage kidney disease within 10 years. Design, setting, participants and measurements To improve identification of patients with poor prognosis we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histological scoring system, we analysed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-MPGN. We used linear regression, survival analysis and Cox proportional hazards models to assess the relationship between histological and clinical parameters with outcome. Results Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane (GBM) double contours and endocapillary hypercellularity. Multivariable analysis showed negative associations between estimated glomerular filtration rate (eGFR) and crescents, interstitial inflammation, and interstitial fibrosis and tubular atrophy (IFTA). Proteinuria positively associated with endocapillary hypercellularity and GBM double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at time of biopsy, and cellular/fibrocellular crescents, segmental sclerosis and IFTA scores. Conclusions Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and IFTA scores were significant determinants of deterioration in kidney function.

Renal anemia is a frequently encountered complication in patients suffering from advanced chronic kidney disease. This is mainly due to the decreased secretion of erythropoietin by the diseased kidneys. The current treatment of renal anemia is based on iron substitution and administration of recombinant erythropoietin. The discovery of HIF (Hypoxia-Inducible Factor) has led to the development of a new class of molecules that block the activity of prolyl-4-hydroxylases and stabilize HIF (Hypoxia-Inducible Factor), a transcription factor that plays an essential role in numerous cellular pathways, including those linked to erythropoiesis and iron metabolism. In this article, we discuss the current understanding of the pathophysiological mechanisms underlying renal anemia and the potential role of the new HIF-stabilizers in its treatment.

High blood pressure levels are frequently encountered in medical practice, whether in an outpatient or inpatient setting. It is imperative to quickly differentiate severe hypertension associated with target organ damage, from severe hypertension without acute organ damage. In the latter situation, the management can be done on an outpatient basis by prescribing oral antihypertensive treatment with a close follow-up. On the other hand, in severe hypertension with acute target organ damage, patients should be admitted in an intensive care unit for close monitoring and, in most cases, treated with intravenous antihypertensive treatment. This article reviews the new definitions and management of these two entities and is addressed to both general practitioner and emergency doctor.

In the last few years, there has been a growing interest in the study of complement, fueleld mainly by the design of complement modulators, especially the C5-blocker eculizumab. The latter has significantly improved the prognosis of some nephropathies, such as the atypical hemolytic uremic syndrome. This breakthrough is a perfect example of fundamental translational research leading to clinical applications for patients. Currently, new molecules are being developed and some of them have already demonstrated clinical efficacy, such as avacopan (C5aR blocker) in ANCA vasculitis. As for kidney transplantation, complement modulators may lead to a new perspective in the treatment of some complications, such as humoral rejection. However, complement modulators carry the side effects, especially the infectious, and high costs.

Over the last decades, an increasing number of cases of chronic and end-stage kidney disease has been observed in Central America and Asia. This kidney disease mainly affects young farmers without classic renal risk factors. The clinical presentation includes a progressive decrease of the glomerular filtration rate, minimal proteinuria and the presence of tubulo-interstitial nephritis at renal biopsy. A close link with global warming is suspected for this disease, called (according to its location) meso-american nephropathy, Sri Lanka nephropathy or chronic kidney disease of unknown etiology. Others have suggested that intake of water contaminated with pesticides may be responsible. This article provides an overview of this new kidney disease. Measures to prevent acute kidney injury during heat waves in Switzerland are also discussed.