Novel avenues for treating diabetic nephropathy: new investigational drugs

<p><b>Introduction</b>: At present, treatment of diabetic kidney disease (DKD) is still mainly based on drugs acting on glycemic and blood pressure control, as there is no validated therapy able to halt the progression of renal failure. Because of the high incidence of DKD, due to the increase of diabetes mellitus in general population, new therapeutic strategies are needed.</p> <p><b>Areas covered</b>: We analysed ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed, dealing with new therapies for DKD.</p> <p><b>Expert opinion</b>: Among the drugs currently being explored, the most promising molecules are those that interfere with glucose-dependent pathways, in particular polyol, protein kinase, hexosamine and AGEs metabolic pathways, and impaired renal vascular regulation. One of the recent goals achieved by molecular biology is the development of monoclonal antibodies able to interfere with extracellular matrix accumulation and fibrosis. Other interesting therapies are under investigation and further studies with a greater number of patients will establish a better approach for diabetic nephropathy.</p

Flow chart of the study.

<p>Flow chart of the study.</p

Multivariable Cox models of determinants of ESRD and all-cause death in the whole study population (n = 2340).

<p>Multivariable Cox models of determinants of ESRD and all-cause death in the whole study population (n = 2340).</p

Carbon and Phosphorus Removal from Primary Municipal Wastewater Using Recovered Aluminum

In this work, recovery of aluminum from coagulated primary sludge and its reuse potential as secondary coagulant were investigated. The recovery process consisted of releasing the particle-bound aluminum from primary sludge by acidification (HCl or H₂SO₄), followed by separation using centrifugation for dissolved coagulant recovery. The recovered coagulant was then reused for treating primary wastewater and overall coagulation efficiency was determined. While with fresh alum, the removal efficiencies of total suspended solids, chemical oxygen demand, total phosphorus, and total nitrogen were 85%, 65%, 80% and 33%, respectively, a drop in removal efficiency of total suspended solids and chemical oxygen demand was observed for recovered aluminum (85–60% and 65–50%, respectively). Nitrogen concentration remained almost constant with each cycle, while phosphorus in the effluent increased by 1 mg/L and 3 mg/L in the first and second cycle, respectively. Precipitation of various aluminum species was modeled for determining the recovery potential of aluminum at low pH. Preliminary cost analysis indicates that optimum recovery of aluminum occurred at a pH of 1.5 for both acids. Struvite precipitation effectively removed increased phosphorus solubilized by acidification at the end of second cycle, however, it also decreased the amount of aluminum available for recycle

Basal characteristics of patients overall and in the two study groups.

<p>Basal characteristics of patients overall and in the two study groups.</p

Adjusted hazard ratios (solid line) and 95% confidence intervals (dashed lines) of one-unit increase of serum phosphorus (P) by 24h proteinuria in the prediction of ESRD in control patients.

<p>The horizontal line represents hazard ratio 1. Beta value of the interaction P*Proteinuria is -0.050 (P 0.004). Hazards are stratified by cohort and CKD stage and adjusted for all covariates in Cox model reported in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0172241#pone.0172241.t005" target="_blank">Table 5</a>.</p

Cumulative incidence probability of ESRD and all-cause death before ESRD, by competing risk analysis, in LP (top) and CON (bottom) patients.

<p>P values were <0.0001 and 0.002 in LP and CON, respectively.</p

Multivariable Cox models of determinants of ESRD and all-cause death in LP patients.

<p>Multivariable Cox models of determinants of ESRD and all-cause death in LP patients.</p

Cumulative incidence probability of ESRD and all-cause death before ESRD, by competing risk analysis, in the whole study population (n = 2340).

<p>P <0.0001.</p

Effect of cumulative exposure to piroxicam, meloxicam, ketorolac and NSAIDs as a whole among current users on the CKD risk.

<p>NSAID = non-steroidal anti-inflammatory drug; ID = index date; OR = odds ratio. OR was adjusted for malignant neoplasm, ischemic heart disease, diabetes mellitus, liver disease, gout, dyslipidemia, hypertension, cerebrovascular disease, lupus erythematosus systemic (LES), amyloidosis, vasculitis, myeloma, polycystic kidney, prior use of nephrotoxic drugs (other than NSAIDs).</p