Franz Volhard: 150th Birth Anniversary of a Father of Nephrology and Hypertension.

Franz Volhard (May 2, 1872, to May 24, 1950) was a German clinician and researcher who made outstanding contributions to the field of nephrology and hyper-tension. His studies led to important developments in knowledge about the pathophysiology of the kidney and its relationship to cardiovascular disease. He contributed to a better understanding of the mechanisms underlying renovascular hypertension by explaining the crucial relationship between the decrease in renal blood flow and the increase in blood pressure. He also introduced a precise classification of the different types of hypertension and the associated renal involvement. In collaboration with Karl Theodor Fahr (1877-1945), he developed a new classification of Bright's disease (nephritis), which was published in the book Die Brightsche Nierenkrankheit. Klinik, Pathologie und Atlas, and revolutionized the concepts behind the mechanisms of glomerulonephritis. During his distinguished career, Volhard headed departments of internal medicine at the Luisenhospital in Dortmund (1905-1910) and in Mannheim (1910-1918). In 1918, he became chairman of the Department of Internal Medicine at the University of Halle, his alma mater, until 1928, the same year he became chairman of the Department of Internal Medicine at the University of Frankfurt until 1938. Volhard continued his successful career until 1950, when he died of complications from a car accident. The worldwide medical com-munity greatly appreciated Franz Volhard's scientific contribution. The International Society of Hypertension posthumously presented him with the "Franz Volhard Award." The aim of this article is to commemorate the importance of this giant of nephrology 150 years after his birth.

The Mysterious Life of Jeronimus Ruscelli and His Contribution to Nephrology (1504-1566).

Jeronimo Ruscelli was a mysterious humanist of great fame. He was born in Viterbo between 1504 and 1518 and died in Venice in 1566. Very little is known about Ruscelli's life, but based on his extensive literary output we can assume that he was endowed with remarkable intellectual abilities and a propensity for varied interests. At a young age, he developed a strong interest in classical studies and attended the court of Cardinal Marini Grimani in Utini. After completing his studies at the University of Padua, he participated in the founding of a humanist academy, the Accademia degli Sdegnati (the Scornful Academy). After his fruitful experience in Rome, he moved to the Neapolitan residence of Marquis Alfonso D'Avalos. Here, Ruscelli founded an "Academy of Secrets", composed of a group of humanists and nobles who had an extensive culture and had different experiences but similar interests. During these productive years, under the pseudonym Alexius Pedemontanus, he wrote one of his masterpieces, The Secreti, an important historical documentary manual of great value. In this book, the author proposes therapies for a wide variety of diseases, claiming in most cases that they have been experimentally and successfully tested in the presence of witnesses in at least 3 clinical cases. Ruscelli composed an extensive version of The Secreti, the Secreti Novi. In this book he reported more than a thousand recipes, the substances used were of a great variety and sometimes curious. According to Ruscelli, the recipes in this updated version of the book were "easy for anyone to make, of little effort, and useful for all kinds of people." The topics of this masterpiece range from general medical suggestions to more specific indications, with a wide variety of recipes and treatments of nephrological and urological interest.

Horseshoe Kidney: 500 Years From the First Report in the Literature.

Horseshoe kidney or ren arcuatus is the most common renal fusion anomaly, with an incidence of 1:500 in the normal population and a male predominance of 2:1. In >90% of cases, the fusion occurs along the inferior pole. It may vary in location, orientation, and arterial and venous anatomy. In 1522, Berengario da Carpi described this renal malformation for the first time in his masterpiece "Isagogae breves" (Introduction to Anatomy). He reported the results of a postmortem examination in the public autopsy room of the University of Bologna, describing "kidneys that are continuous as if they were a kidney, with two emulsifying veins, two emulsifying arteries, two ureteral outlets." In 1564, Leonardo Botallo described and illustrated the features of this atypical anatomical representation, and later, in 1602, Leonard Doldius added further details by examining this anatomical feature during an autopsy. In 1761, Giovanni Battista Morgagni discussed this condition not only as a rare anatomical curiosity found only in necroscopy but also discussed its physiological aspect. In the nineteenth century, with the advent of renal surgery, the horseshoe kidney played a more important role in urological diagnosis and treatment, and its identification became more frequent. With the advent of pyelography, imaging reports of the horseshoe kidney allowed a more accurate representation of the anatomical variants, which was particularly useful in preoperative assessment and outcomes. Berengario da Carpi laid the foundation for a better knowledge of this anatomical anomaly. Five hundred years after the first report in the literature, relevant advances have been made in the management of complications associated with horseshoe kidney and in diagnosis, confirming the need to monitor individuals with this condition who are at higher risk of developing chronic kidney disease.

Cystic Fibrosis: A Risk Condition for Renal Disease.

OBJECTIVE: Cystic fibrosis (CF) is the most common autosomal recessive disease affecting the Caucasian population, with a birth incidence ranging between 1:2,500 and 1:1,800. It is caused by mutations in the CF transmembrane regulator gene which is localized on 7 chromosomes. Renal disease is reported as a relatively rare complication in adult patient with CF. We evaluated proteinuria and chronic renal failure (CRF) in a population of patients with CF. METHODS: A retrospective study was carried out in a referral center for CF at University of Messina in Italy. We identified all patients with renal disease, characterized by proteinuria and/or CRF, during the period 2007 to 2012 and reviewed their medical records to assess influence on renal disease of genotype, number of pulmonary exacerbation, pancreatic insufficiency, pulmonary function, CF-related diabetes, and antibiotics courses. RESULTS: From a population of 77 adult patients with CF, we identified 9 patients with proteinuria (11.7%), and 11 patients (14.28%) with CRF. Mean age was 35.6 (+5.1 standard deviation) years, 55% were female and 33% had diabetes mellitus. Renal biopsy was performed in 3 patients because of nephrotic syndrome in 1 patient and proteinuria with renal failure in the other 2 patients. Renal amyloidosis was disclosed in 2, whereas IgA nephropathy in 1 patient. The ΔF508 mutation in homozygosis was present in 44% of patients with proteinuria (vs. 27% of our CF population, relative risk 2.07), whereas genotype ΔF508/N1303K in 22%. ΔF508 allele mutation was present in 77.7% of proteinuric patients. CONCLUSIONS: Our study shows a higher prevalence of renal disease in patients with CF, than was previously described. The main reason may be related to increased life expectancy because of better management. Moreover, patients with ΔF508 homozygosis had higher risk of proteinuria.

The management of kidney stones as suggested by Goeury-Duvivier.

The management of kidney stones has always been a big problem for doctors of all time. Goeury Duvivier in his masterpiece "Guide des malades atteints daffections de voie urinaires ou des organes de la gnration chez lhomme et chez la femme shows us the different kind of diseases which affects the urinary tract and in particular highlights the list of the main methods that during the history characterized the treatment of renal calculi. Duvivier gives us the descriptions of invasive innovative techniques of the time, the Taille, the Lithotripsy and Lithotomy and their negative effects or limits for each technique. He also describes the different kind of palliative methods used in the 19th century to treat renal lithiasis and the clinical case reports of the time.

Vitamin D receptor polymorphism in chronic kidney disease patients with complicated cardiovascular disease.

Several studies indicate a relationship between vitamin D and cardiovascular disease. Pleiotropic actions of vitamin D and its analogs are mediated by vitamin D receptor (VDR). VDRs have been identified in almost all tissues, including vascular smooth muscle cells, cardiomyocytes, and endothelial cells. The FokI and BsmI polymorphisms of the VDR gene are regarded as strong markers of disturbed vitamin D signaling pathway. Studies investigating the relationship between VDR genotypes and left ventricular hypertrophy revealed a highly significant association with the BsmI Bb heterozygous genotype. There are conflicting data on the action of vitamin D in left ventricular hypertrophy. Experimental as well as observational studies and small clinical trials have suggested that vitamin D administration may favorably influence left ventricular hypertrophy, whereas large randomized clinical trials have shown negative results. However, a beneficial effect on the left atrial volume index and the duration of hospitalization were observed in patients treated with vitamin D analogs. Larger clinical trials with robust clinical end points are needed to confirm that vitamin D is effective in preventing cardiovascular disease in chronic kidney disease patients and in general population.

Erythropoiesis-stimulating agents: dose and mortality risk.

Hypo-responsiveness to erythropoiesis-stimulating agents (ESAs) has been associated with increased mortality in end-stage renal disease patients. It is not clear if this effect is related to the elevated ESAs dosage for targeting hemoglobin levels or underlying morbid conditions that lead to ESA resistance. We retrospectively evaluated from 2008 to death or December 2011, 28 consecutive incident hemodialysis patients. We identified 2 cohort of patients based on their mean annual ESAs dosage. The correlation between data was evaluated with the Spearman's rho test. Kaplan-Meier curves were generated to assess survival in subjects with high and low ESAs mean dose. Median ESAs dosage, used as a cutoff point between patients at high and low ESAs dose, was at 11.000 IU/week for epoetin alfa and beta, 55 mcg/week for darbopoietin, and 220 mcg/month for cera. Mean hemoglobin (Hb) level was 10.58 ± 0.13 g/dL. Of 28 patients, during follow-up, 6 (21,4%) died of all causes. High-dose ESA therapy was associated with increased all-cause mortality (P = .047). Moreover, there was a negative correlation between ESAs dose and Hb levels (rho = -0.825; P < .001). Higher ESAs dose for the treatment of anemia in incident hemodialysis patients was associated with higher mortality risk. ESAs and Hb serum levels were inversely correlated with mortality. Together, these findings suggest that ESAs dosage and Hb level may play a role through an independent manner or an interactive effect that adversely affects mortality.

Sexual dysfunction in women with diabetic kidney.

Few studies address alteration of sexual function in women with diabetes and chronic kidney disease (CKD). Quality of life surveys suggest that discussion of sexual function and other reproductive issues are of psychosocial assessment and that education on sexual function in the setting of chronic diseases such as diabetes and CKD is widely needed. Pharmacologic therapy with estrogen/progesterone and androgens along with glycemic control, correction of anemia, ensuring adequate dialysis delivery, and treatment of underlying depression are important. Changes in lifestyle such as smoking cessation, strength training, and aerobic exercises may decrease depression, enhance body image, and have positive impacts on sexuality. Many hormonal abnormalities which occur in women with diabetes and CKD who suffer from chronic anovulation and lack of progesterone secretion may be treated with oral progesterone at the end of each menstrual cycle to restore menstrual cycles. Hypoactive sexual desire disorder (HSDD) is the most common sexual problem reported by women with diabetes and CKD. Sexual function can be assessed in women, using the 9-item Female Sexual Function Index, questionnaire, or 19 items. It is important for nephrologists and physicians to incorporate assessment of sexual function into the routine evaluation protocols.

Vitamin D receptor gene polymorphism and left ventricular hypertrophy in chronic kidney disease.

FokI and BsmI polymorphisms of vitamin D receptor (VDR) gene are regarded as reliable markers of disturbed vitamin D signaling pathway. Left ventricular hypertrophy (LVH) is a strong cardiovascular risk marker in end stage renal disease (ESRD) patients. Since BsmI polymorphism has been associated with LVH in ESRD patients, we addressed this study in patients with chronic kidney disease (CKD) not yet on dialysis. One hundred and forty five patients with CKD stage 3 were genotyped for FokI and BsmI VDR polymorphisms, in order to assess the relationships between these VDR polymorphisms, some markers of mineral bone disorders, and LVH measured by echocardiography. Patients bearing either the Ff heterozygous or FF homozygous genotype had significantly higher PTH values than those bearing the ff genotype. The relationships between VDR genotypes and LVH revealed a highly significant association of the BsmI Bb heterozygous genotype with LVH. In patients with CKD stage 3 BsmI B allele was independently related to LVH. Since LVH is a frequent finding in dialysis population due to several mechanisms, the presence of the same relationship in patients with CKD strengthens the hypothesis that alterations of vitamin D signaling are implicated in LVH development in patients with renal diseases.

Vitamin D metabolism and activity as well as genetic variants of the vitamin D receptor (VDR) in chronic kidney disease patients.

For a long time, the role of vitamin D in chronic kidney disease (CKD) received less attention than treating vitamin D metabolism disorders. Low active vitamin D levels represent one of the most important factors in the pathophysiology of secondary hyperparathyroidism. For this reason, the administration of active vitamin D compounds is commenced during the course of CKD treatment. Moreover, patients with CKD exhibit a high prevalence of hypovitaminosis of 25-hydroxyvitamin D (25[OH]D) unrelated to vitamin D intake. However, several studies have recently advanced our knowledge about the effects of both the 25(OH)D and 1,25(OH)2D forms of endogenous vitamin D and the possible beneficial effects of vitamin D treatment. These studies add to the already well-known effects of vitamin D on mineral metabolism. Several studies have hypothesized a link between reduced levels of 25-OH D and a greater cardiovascular risk in the general population. Another important aspect of vitamin D metabolism is the existence of polymorphic genetic variants of the vitamin D receptors (VDRs). Most studies have aimed to determine whether VDR polymorphisms are involved in the development of secondary hyperparathyroidism (sHPT).

An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts.

In 2006, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines introduced, for the first time, the definition and diagnostic and therapeutic criteria for a systemic complication of the mineral metabolism dysfunction, such as vascular calcification, caused by chronic renal insufficiency. Abdominal x-ray and echocardiography rather than the more complex CT scan is suggested to make the diagnosis. This condition is associated with high cardiovascular risk and consequent poor prognosis. An alteration in total body calcium (Ca) content is one of the key factors in the cardiovascular complications observed in uremic subjects. In the general population, the addition of Ca to the diet has been to shown to improve bone mineral density (BMD) compared to controls, but it does not appear to reduce the risk of bone fractures. In patients with CKD, there are certainly some theoretical justifications for administering calcium salts: vitamin D deficiency, which reduces the intestinal absorption of Ca; hypocalcemia, which increases the risk of hyperparathyroidism; and hyperphosphatemia, which justifies the use of Ca-based P binders. There is already a large body of evidence pointing against the use of Ca-based binding agents, when there is a positive Ca balance because of the development of vascular calcification.