Hypertension

Hypertension (HTN) is a common condition and a risk factor for numerous comorbidities, including cardiovascular disease, cerebrovascular disease, and progressive renal disease. In many people the aetiology of HTN is unknown, but in some a triggering “secondary” cause can be identified, e.g. renal disease, endocrine, or other underlying condition. For most people the treatment of HTN is straightforward, but in a small number the blood pressure can become “malignant or accelerated” and require urgent treatment or hospitalization. The chapters in this section provide an overview of the clinical assessment and investigation of a hypertensive patient, the recommended lifestyle modifications and pharmacological treatment options available, and potential complications of HTN. Renal artery stenosis a common cause of HTN that can be caused by atheromatous renovascular disease (ARVD) or other rarer pathologies, including fibromuscular disease, Takayasu’s arteritis, or other syndromes. ARVD is the commonest cause of renal artery disease in the Western world and in this section the authors focus upon the epidemiology and clinical presentation of ARVD and the potential diagnostic and treatment strategies. A particular focus is given to the role of medical and interventional treatment of ARVD, including potential outcomes, complications, and prognosis.

miR-196b-5p-enriched extracellular vesicles from tubular epithelial cells mediated aldosterone-induced renal fibrosis in mice with diabetes

IntroductionAldosterone is a mediator of progressive renal disease, but the mechanisms for aldosterone-mediated renal impairment in mice with diabetes are not fully defined.MethodsAldosterone and/or mineralocorticoid receptor antagonist eplerenone were used to treat the db/db mice with diabetes. Proximal tubule epithelial cells (PTECs) and fibroblasts were cultured. Blood and kidney samples from patients with diabetes with or without diabetic kidney disease (DKD) were used to verify the findings from animals and cultured cells.ResultsWe found that aldosterone promoted proteinuria and tubulointerstitial extracellular matrix (ECM) accumulation in db/db mice with diabetes while eplerenone mitigated the adverse effect of aldosterone. However, coculture of PTECs and fibroblasts found that when PTECs-derived extracellular vesicles (EVs) were taken up by fibroblasts, ECM production increased remarkably. Moreover, C57BL/6 mice injected with EVs from renal cortex of aldosterone-treated db/db mice showed increased ECM accumulation. Function of the ingredients of PTECs-derived EVs were analyzed, and RNAs were identified to be responsible for the EVs-induced fibroblast dysfunction. Furthermore, microRNA (miRNA) array analysis revealed that miR-196b-5p was the most remarkably increased miRNA in PTECs-derived EVs with aldosterone stimulation. Overexpression of miR-196b-5p in fibroblasts increased ECM production, accompanied by inhibition of the SOCS2 expression and enhanced STAT3 phosphorylation. In addition, plasma levels of miR-196b-5p was higher in patients with DKD as compared with patients without DKD and miR-196b-5p levels positively correlated with the albuminuria concentration. In kidney specimens from patients with diabetes, expression of miR-196b-5p, located mainly in PTECs, increased in patients with DKD as compared with the non-DKD.ConclusionThis study demonstrates the involvement of miR-196b-5p-EVs pathway as a novel mechanism in aldosterone-induced renal fibrosis in diabetes. EVs rich in miR-196b-5p mediate the crosstalk between PTECs and fibroblast during the development of renal fibrosis, which might be associated with STAT3/SOCO2 signaling pathway.

Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments

Renal fibrosis is the common pathway for most forms of progressive renal disease. The Unilateral Ureteral Obstruction (UUO) model is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow. Furthermore, experimental UUO in rodents is believed to mimic human chronic obstructive nephropathy in an accelerated manner. Renal fibrosis is the common pathway for most forms of progressive renal disease. Removing the obstruction may not be sufficient to reverse fibrosis, so an accompanying treatment may be of benefit. In this review, we have done a revision on treatments shown to ameliorate fibrosis in the context of the UUO experimental model. The treatments inhibit the production of fibrotic and inflammatory proteins such as Transforming Growth Factor β1 (TGF-β1), Tumor Necrosis Factor α (TNF-α), collagen and fibronectin, Heat Shock Protein 47 (HSP47), suppress the proliferation of fibroblasts, prevent epithelial-to-mesenchymal transition, reduce oxidative stress, inhibit the action of the Nuclear Factor κB (NF-κB), reduce the phosphorylation of mothers against decapentaplegic homolog (SMAD) family members 2 and 3 (Smad2/3) or Mitogen-Activated Protein Kinases (MAPKs), inhibit the activation of the renin-angiotensin system. Summaries of the UUO experimental methods and alterations observed in the UUO experiments are included.

Proteinuria and cholesterol reduction are independently associated with less renal function decline in statin-treated patients; a post hoc analysis of the PLANET trials

Background Statins have shown multiple effects on different renal risk factors such as lowering of total cholesterol (TC) and lowering of urine protein:creatinine ratio (UPCR). We assessed whether these effects of statins vary between individuals, the extent of discordance of treatment effects on both TC and UPCR within an individual, and the association of responses in TC and UPCR with estimated glomerular filtration rate (eGFR) decline. Methods The PLANET I and II (Renal effects of Rosuvastatin and Atorvastatin in Patients Who Have Progressive Renal Disease) trials examined effects of atorvastatin and rosuvastatin on proteinuria and renal function in patients with proteinuria. We post hoc analysed 471 therapy-adherent proteinuric patients from the two trials and assessed the individual variability in UPCR and TC response from 0 to 14 weeks and whether these responses were predictive of eGFR decline during the subsequent 9 months of follow-up. Results UPCR and TC response varied between individuals: mean UPCR response was −1.3% (5th–95th percentile −59.9 to 141.8) and mean TC response was −93.9 mg/dL (−169.1 to −26.9). Out of 471 patients, 123 (26.1%) showed a response in UPCR but not in TC, and 96 (20.4%) showed a response in TC but not in UPCR. eGFR (mL/min/1.73 m2) did not decrease significantly from baseline in both UPCR responders [0.4; 95% confidence interval (CI) −1.6 to 0.9; P = 0.54] and TC responders (0.3; 95% CI −1.8 to 1.1; P = 0.64), whereas UPCR and TC non-responders showed a significant decline in eGFR from baseline (1.8; 95% CI 0.6–3.0; P = 0.004 and 1.7; 95% CI 0.5–2.9; P = 0.007, respectively). A lack of response in both parameters resulted in the fastest rate of eGFR decline (2.1; 95% CI 0.5–3.7; P = 0.01). These findings were not different for rosuvastatin or atorvastatin. Conclusions Statin-induced changes in cholesterol and proteinuria vary between individuals and do not run in parallel within an individual. The initial fall in cholesterol and proteinuria is independently associated with a reduction in eGFR decline. This highlights the importance of monitoring both cholesterol and proteinuria after initiating statin therapy.

Treatment of Acute Urinary Tract Infection in Children with Pipemidic Acid

Urinary tract infection in children is still an important problem in uronephrology. The disease.tends to develop recurrently and results in chronic progressive renal disease in the future. Pipemidic acid is a bactericidal quinolone derivate, with a wide spectrum against gram positive and negative bacteria. Compared with nalidixic acid, pipemidic acid proves to be more effective against Pseudomonas, E. coli, Alkali genes and Salmonella. Thirty one cases with acute urinary tract infection had been studied descriptively. The etiology revealed as follows: E. coli (45.2%), Alkaligenes (16.2%), Enterobacter (9.6%), Staphylococcus (9.6%), Pseudomonas (9.6%), Paracolon (6,5%), and Proteus (3.3%). Pipemidic acid was administered orally to these patients, 15-20 mg/kg/day divided in 2 equal doses for 10 days. Bacteriological examinations was repeated on the 6th day and 11th day treatment. The result revealed that on the 6th day of treatment, in 27 patients (87, 09%) there was no bacteriuria while on the 11th day the urine of 29 patients (93.54%) were sterile. In conclusion, a 5 day treatment of acute urinary tract infection in children with pipemidic acid is quite effective.