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Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephritis seen primarily in countries in the Balkan Peninsula. The disease, which was first described in Romania 50 years ago, often manifests as a form of chronic nephritis that is also associated with upper urothelial cancers (UUC). This review summarizes the observations and studies performed in Romania regarding this disease during the last 50 years with particular emphasis on Mehedinti county. The paper analyzes current data on the epidemiology of the disease in this area, specifically in relation to the observations made in dialysis centers in the same area. It also discusses the diagnostic criteria of patients with BEN stemming from collaborations between specialists working in other countries affected by the disease. Moreover, the paper analyzes the main etiological factors suspected to play a role in BEN: aristolochic acid (the disease has many similarities to aristolochic nephropathy caused by Chinese herbs), mycotoxins, toxic substances from pliocene lignite, genetic factors, and viruses. Studies performed by Romanian authors are presented briefly in comparison to studies performed by other authors. Finally, given that BEN is an important health problem in the region, the relationship between BEN and UUC is further analyzed.

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Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) that primarily has an antiproteinuric effect and is used for the treatment of chronic glomerular diseases. In chronic glomerular disease (CGD), proteinuria is involved in the production of tubulo-interstitial lesions and has an important role in their progression. CGD improves with steroid therapy and immunosuppression. In the case of a favorable outcome, a reduction in proteinuria is also attained. In some situations, this therapy is prohibited, requiring alternative medication. NSAIDs are one class of these alternative drugs; in addition to having anti-inflammatory actions, they also have antiproteinuric effects. The aim of the study has been to assess the effect of the anti-inflammatory treatment with meloxicam upon proteinuria as well as upon tubular lesions by determining urinary NAG in its dynamics. The study was performed on 12 patients with CGD, 6 of them with nephrotic syndrome. On all patients we administered treatment with meloxicam 15 mg/day, 30 days. On all patients we performed proteinuria and urinary N-acetyl b D glucosaminidase (NAG) at the beginning, after 7 days and after 30 days of treatment. A 24-hour urine collection was taken from all patients. The urinary protein concentration was determined with the use of the Dimension (Dade Behring, Inc., Newark, DE, USA) clinical chemistry system UCFP method. We found a decrease of proteinuria under treatment from 2.85 +/- 1.69 g/24h to 1.53 +/- 0.83 g/24h, which was significantly lower, compared to the initial measurement (p = 0.01878). After 30 days of treatment with meloxicam, urinary NAG decreased from 10.6 +/- 12.56 U/g creatinine to 6.44 +/- 7 U/g, a decrease that was statistically non-significant. We observed a strong correlation between initial urinary NAG and initial proteinuria ri = 0.924, p < 0.001 and between final urinary NAG and final proteinuria rf = 0.856, p < 0.001. Our study revealed the favorable effect of meloxicam on patients with CGD on a 30-day treatment phase reflected on the evolution of proteinuria. Only in one case we did reveal a possible deleterious effect of this treatment. The assessment of the effect on tubulo-interstitial lesions in this short treatment period through urinary NAG assessment indicated only a modest and statistically non-significant response. We consider that meloxicam can be a useful drug in the treatment of proteinuric glomerular diseases.

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Renal diseases induce nephroprotective measures that may affect the heart, brain and other organs. In addition, many cardiovascular and neurological diseases are accompanied by renal lesions. For these reasons, multiorgan-protective measures, including cardio-, reno- and neuro-protective measures, are necessary to treat these diseases. The drugs used in nephrology are often pleiotropic. Although they usually address a single organ or tissue, many of them have complex actions that may provide multiorgan-protection. The present paper aims to review 3 classes of drugs that are commonly prescribed in nephrological practice: statins, RAS blockers (such as ACEIs and ARBs) and erythropoietin (EPO). This paper highlights the renoprotective actions, as well as those that are protective of the heart, brain and other organs, of these drugs at the cellular and molecular level. Their protective actions are attributable to their main effects and pleiotropic effects. The protective pleiotropic actions of these drugs may be exerted on multiple organs, making them multiorgan-protective. Another objective is to analyse the shared multiorgan-protective pleiotropic effects of RAS blockers (ACEIs and ARBs), statins and erythropoietin. This will allow for the practical association of the main renoprotective drugs with multiorgan protection.

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