Chronic dehydration induces injury pathways in rats, but does not mimic histopathology of chronic interstitial nephritis in agricultural communities.

CINAC-patients present renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic dehydration as a major etiological factor for CINAC. Here, we evaluated histological and molecular changes in dehydrated versus toxin exposed rats.

Metformin and Canagliflozin Are Equally Renoprotective in Diabetic Kidney Disease but Have No Synergistic Effect.

Diabetic Kidney Disease (DKD) is a major microvascular complication for diabetic patients and is the most common cause of chronic kidney disease (CKD) and end-stage renal disease. Antidiabetic drugs, such as metformin and canagliflozin, have been shown to exert renoprotective effects. Additionally, quercetin recently showed promising results for the treatment of DKD.

Progression of established non-diabetic chronic kidney disease is halted by metformin treatment in rats.

Current treatment strategies for chronic kidney disease (CKD) mainly focus on controlling risk factors. Metformin, a first-line drug for type 2 diabetes, exerts beneficial pleiotropic actions beyond its prescribed use and incipient data have revealed protective effects against the development of kidney impairment. This study evaluated the therapeutic efficacy of metformin and canagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor recently approved by the United States Food and Drug Administration to treat diabetic nephropathy, in slowing the progression of established non-diabetic CKD.

L-NAME Administration Enhances Diabetic Kidney Disease Development in an STZ/NAD Rat Model.

One of the most important risk factors for developing chronic kidney disease (CKD) is diabetes. To assess the safety and efficacy of potential drug candidates, reliable animal models that mimic human diseases are crucial. However, a suitable model of diabetic kidney disease (DKD) is currently not available.

Haemodynamic frailty - A risk factor for acute kidney injury in the elderly.

Clinical frailty in the elderly is defined by a composite measure of functional psychomotor decline. Herein, we develop the concept of haemodynamic frailty (HDF), a state of increased predisposition to disease prevalent in the elderly and characterised by impairment of the network of compensatory responses governing the defence of circulatory volume and adaptive haemodynamic function. We review the factors predisposing the elderly to HDF, with a focus on the impaired capacity to sustain total body water balance.

Chronic interstitial nephritis in agricultural communities: a new perspective on etiology, diagnosis and mechanism.

Chronic interstitial nephritis in agricultural communities is a devastating kidney disease with a globally increasing prevalence. Its cause is unknown. Two predominant etiologies are hypothesised: recurrent episodes of dehydration and exposure to environmental toxins, such as agrochemicals and metals.

Renoprotective effects of sucroferric oxyhydroxide in a rat model of chronic renal failure.

Introduction: Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease-mineral and bone disorder (CKD-MBD) rat model.

Methods: To induce stable renal failure, rats were administered a 0.

Chronic interstitial nephritis in agricultural communities is a toxin-induced proximal tubular nephropathy.

Almost 30 years after the detection of chronic interstitial nephritis in agricultural communities (CINAC) its etiology remains unknown. To help define this we examined 34 renal biopsies from Sri Lanka, El Salvador, India and France of patients with chronic kidney disease 2-3 and diagnosed with CINAC by light and electron microscopy. In addition to known histopathology, we identified a unique constellation of proximal tubular cell findings including large dysmorphic lysosomes with a light-medium electron-dense matrix containing dispersed dark electron-dense non-membrane bound "aggregates".

Human health risk associated with the management of phosphorus in freshwaters using lanthanum and aluminium.

The use of geo-engineering materials to manage phosphorus in lakes has increased in recent years with aluminium and lanthanum based materials being most commonly applied. Hence the potential impact of the use of these compounds on human health is receiving growing interest. This review seeks to understand, evaluate and compare potential unintended consequences on human health and ecotoxicological risks associated with the use of lanthanum- and aluminium-based materials to modify chemical and ecological conditions in water bodies.

Metformin: A Candidate Drug for Renal Diseases.

Over the past decades metformin has been the optimal first-line treatment for type 2 diabetes mellitus (T2DM). Only in the last few years, it has become increasingly clear that metformin exerts benign pleiotropic actions beyond its prescribed use and ongoing investigations focus on a putative beneficial impact of metformin on the kidney. Both acute kidney injury (AKI) and chronic kidney disease (CKD), two major renal health issues, often result in the need for renal replacement therapy (dialysis or transplantation) with a high socio-economic impact for the patients.

Short-term dexamethasone treatment transiently, but not permanently, attenuates fibrosis after acute-to-chronic kidney injury.

Background: Acute kidney injury (AKI) is an underestimated, yet important, risk factor for the development of chronic kidney disease (CKD). Persistence of inflammation after a renal ischemic injury has been observed, both in experimental models and patients, and is thought to be an important mechanisms underlying progression of acute-to-chronic renal injury. Temporary suppression of inflammation immediately after AKI might therefore be a good first-line therapeutic strategy towards a better long term outcome.

Epithelial Cell Cycle Behaviour in the Injured Kidney.

Acute kidney injury (AKI), commonly caused by ischemia-reperfusion injury, has far-reaching health consequences. Despite the significant regenerative capacity of proximal tubular epithelium cells (PTCs), repair frequently fails, leading to the development of chronic kidney disease (CKD). In the last decade, it has been repeatedly demonstrated that dysregulation of the cell cycle can cause injured kidneys to progress to CKD.

Environmental toxin-induced acute kidney injury.

Human beings are exposed to various potentially toxic agents and conditions in their natural and occupational environments. The kidney, due to its concentrating ability and excretory function, is highly vulnerable to the effects of environmental toxins. Identifying the precise cause and mechanisms of environmentally induced renal injury remains a challenge for which various scientific disciplines need to be involved.

Untargeted DNA-Demethylation Therapy Neither Prevents Nor Attenuates Ischemia-Reperfusion-Induced Renal Fibrosis.

Background: Current treatment options for chronic kidney disease (CKD) are limited and their focus is on slowing its progression by addressing comorbidities. Fibrosis, the common histopathological process in CKD, is a major therapeutic research target. In CKD, fibroblasts are terminally activated due to alterations in their DNA-methylation pattern, particularly hypermethylation.

Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment.

Evaluation of intestinal phosphate binding to improve the safety profile of oral sodium phosphate bowel cleansing.

Prior to colonoscopy, bowel cleansing is performed for which frequently oral sodium phosphate (OSP) is used. OSP results in significant hyperphosphatemia and cases of acute kidney injury (AKI) referred to as acute phosphate nephropathy (APN; characterized by nephrocalcinosis) are reported after OSP use, which led to a US-FDA warning. To improve the safety profile of OSP, it was evaluated whether the side-effects of OSP could be prevented with intestinal phosphate binders.

Lanthanum carbonate inhibits intestinal oxalate absorption and prevents nephrocalcinosis after oxalate loading in rats.

Purpose: Increased intestinal oxalate absorption leads to increased urinary oxalate excretion (secondary hyperoxaluria) and calcium oxalate crystal formation, contributing to nephrocalcinosis/lithiasis. Lanthanum carbonate is an intestinal phosphate binder that is orally administered to patients on dialysis to treat hyperphosphatemia. It is hypothesized that lanthanum can also bind oxalate, in addition to phosphate.

Arterial microcalcification in atherosclerotic patients with and without chronic kidney disease: a comparative high-resolution scanning X-ray diffraction analysis.

Vascular calcification, albeit heterogeneous in terms of biological and physicochemical properties, has been associated with ageing, lifestyle, diabetes, and chronic kidney disease (CKD). It is unknown whether or not moderately impaired renal function (CKD stages 2-4) affects the physiochemical composition and/or the formation of magnesium-containing tricalcium phosphate ([Ca,Mg](3)[PO(4)](2), whitlockite) in arterial microcalcification. Therefore, a high-resolution scanning X-ray diffraction analysis (European Synchrotron Radiation Facility, Grenoble, France) utilizing histological sections of paraffin-embedded arterial specimens derived from atherosclerotic patients with normal renal function (n = 15) and CKD (stages 2-4, n = 13) was performed.

Hyperoxaluria: a gut-kidney axis?

Hyperoxaluria leads to urinary calcium oxalate (CaOx) supersaturation, resulting in the formation and retention of CaOx crystals in renal tissue. CaOx crystals may contribute to the formation of diffuse renal calcifications (nephrocalcinosis) or stones (nephrolithiasis). When the innate renal defense mechanisms are suppressed, injury and progressive inflammation caused by these CaOx crystals, together with secondary complications such as tubular obstruction, may lead to decreased renal function and in severe cases to end-stage renal failure.

The tubular epithelium in the initiation and course of intratubular nephrocalcinosis.

Intratubular nephrocalcinosis is defined as the histological observation of calcium oxalate and/or calcium phosphate deposits retained within the lumen of the renal tubules. As the tubular epithelium is the primary interaction partner of crystals formed in the tubular fluid, the role of the epithelial cells in nephrocalcinosis has been investigated intensively. This review summarizes our current understanding on how the tubular epithelium mechanistically appears to be involved both in the initiation and in the course of nephrocalcinosis, with emphasis on in vivo observations.

Crystalluric and tubular epithelial parameters during the onset of intratubular nephrocalcinosis: illustration of the 'fixed particle' theory in vivo.

Background: The 'fixed particle' theory states that, besides crystal formation in the tubular fluid, crystal adhesion to the tubular epithelium is a prerequisite for the development of intratubular nephrocalcinosis. It has been hypothesized that the tubular epithelium, in order to bind crystals, needs to be phenotypically altered. Whereas most evidence hereto is provided by in vitro experiments, we set out to illustrate this theory in vivo.