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. Areas covered: We analysed ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed, dealing with new therapies for DKD. Expert opinion: 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.

Background Evidences show that around 20% of biosimilar or originator erythropoiesis-stimulating agents (ESAs) users are hyporesponsive. Controversial post-marketing data exist on the predictors of ESA hyporesponsiveness. The aim of this study was to identify predictors of ESA hyporesponsiveness in patients with chronic kidney disease (CKD) or cancer in clinical practice. Methods During the years 2009–2015, a multi-center, population-based, cohort study was conducted using claims databases of Treviso and Caserta Local Health Units (LHUs). All incident ESA users were characterized at baseline and the differences between the baseline hemoglobin (Hb) value, that is the Hb registered within 30 days prior to the first ESA dispensing (index date, ID) and each outcome Hb value (registered between 30 and 180 days after ID) were calculated and defined as delta Hb (ΔHb). Incident ESA users were defined as hyporesponsive if, during follow-up, they registered at least one ΔHb < 0 g/dL. Including all potential predictors of ESA hyporesponsiveness and stratifying by indication for use, univariate and multivariate binary logistic regression models and Receiver Operating Characteristic (ROC) curves were carried out. Results `In general, 1080 incident ESA users (CKD: 57.0%; cancer: 43.0%) were identified. In CKD, predictors of ESA hyporesponsiveness were C-reactive protein (OR = 1.2, 95% CI: 1.0–1.5; P-value = 0.060) and high levels of baseline Hb (OR = 1.7, 95% CI: 1.2–2.2; P-value< 0,001), the latter being also predictor of ESA hyporesponsiveness in cancer (OR = 1.7, 95% CI: 1.1–2.4; P-value = 0.007). Both in CKD and in cancer, the type of ESA, biosimilar or originator, was not a predictor of ESA hyporesponsiveness. In CKD, concomitant use of iron preparations (OR = 0.3, 95% CI: 0.2–0.7; P-value = 0.002) and of high dosage of angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers (OR = 0.5, 95% CI: 0.3–0.9; P-value = 0.022) were protective factors against ESA hyporesponsiveness. Conclusions The study confirmed traditional potential predictors of hyporesponsiveness to ESA. The use of biosimilar or originator ESA was not a predictor of hyporesponsiveness in an outpatient setting from two large Italian areas. A better knowledge of the predictors of ESA response would allow a better anemia management to improve patients’ quality of life.

In a general practice of Southern Italy the management of diabetes mellitus changed only marginally in newly diagnosed CKD patients, suggesting a therapeutic inertia on the part of prescribers.

A multidisciplinary approach represents the best method to interact with patients. Neoplastic and renal diseases are closely related to each other because of an increased risk of cancer among individuals with end-stage renal disease and because of the high prevalence of renal failure in cancer patients. Physicians should be able to know how to prevent and treat the possible complications which may appear during the course of neoplastic disease that may lead to kidney damage such as the Acute Tumor Lysis Syndrome, disorders of hydroelectrolitic balance, metabolic alterations in the calcium-phosphorus, anemia, interstitial and glomerular impairment due to chemotherapy. It is very important to know patients' renal function and directly monitor it, before and during treatment, using formulas for estimating glomerular filtration rate (GFR) and above all, specific biomarkers are more early and sensitive than the increase of creatinine, like neutrophil gelatinase-associated lipocalin. Additionally, physician should consider that alteration of GFR or substitutive renal treatments severely influence dosage of tumor markers and it could lead to wrong diagnosis of cancer. The aim of this article is to provide a review of problems related to cancer relevant in the development of renal failure and try to define the best therapeutic strategies to cope with possible kidney imbalances induced by cancer or its treatment.

The impact of water intake has been studied in several renal diseases. For example, increasing water intake is useful to prevent primary and secondary nephrolithiasis. In autosomal dominant polycystic kidney disease, arginine vasopressin (AVP) is involved in the progression of the disease, and water intake could play a therapeutic role by inhibiting the synthesis of AVP, but its efficacy is still controversial. Conversely, the use of aquaretics, which are antagonists of AVP V2 receptors, results in the reduction of the increase rate of total kidney volume with a slower decline of glomerular filtration rate. In chronic kidney disease, AVP contributes to glomerular hyperfiltration, arterial hypertension, and synthesis of renin, resulting in renal sclerosis. Increased water intake could reduce AVP activation determining a potential protective effect on the kidney, but its efficacy has not yet been clearly demonstrated. On the other side, sodium and potassium play an important role in the control of arterial blood pressure and are involved in the development and progression of chronic kidney disease. Reduction of sodium intake and increase of potassium intake determine a decrease of arterial blood pressure with a beneficial effect on the kidney; however, adherence to sodium restriction is very poor. Regarding this, sodium-hydrogen exchanger isoform 3 inhibitors may reduce sodium absorption in the gut. The most recent sodium-hydrogen exchanger isoform 3 inhibitor, known as tenapanor, reduces extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in experimental studies and increases fecal loss of sodium in humans.