Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis.

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using next generation sequencing (NGS) for 5 genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, 9 of them novel. In 5 families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-years, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies.

Comparison of estimated creatinine clearance among five formulae (Cockroft-Gault, Jelliffe, Sanaka, simplified 4-variable MDRD and DAF) and the 24hours-urine-collection creatinine clearance.

BACKGROUND: GFR estimation is of major importance in everyday clinical practice. Usually it is done using one of the many eGFR equations available. In this study we compared in our population four widespread eGFR equations and our own empirical eGFR, with creatinine clearance calculated through a timed urine collection. PATIENTS AND METHODS: We collected laboratory data of 907 patients from our clinic and outpatient department through a ten-year period and statistically compared the eGFR results between them and with the timed urine collection creatinine clearances. RESULTS: All eGFR equations gave acceptable approximations to the timed urine collection creatinine clearances. However, in different subpopulations some equations did better than others, without any clear advantage of any equation overall. Surprisingly, our empirical equation named DAF also gave acceptable approximations regardless of age, weight and sex of the patient. CONCLUSIONS: In our population our empirical eGFR method (DAF) gave satisfactory results regarding the monitoring of renal function, compared with four other eGFR methods. We suggest that it could provide a very fast and easy to use means of eGFR calculation.

HPRT deficiency as the cause of ESRD in a 24-year-old patient: a very rare presentation of the disorder.

A 24-year-old male with end-stage renal disease (ESRD) and disproportionately high uric acid plasma concentration was admitted to our unit. After studying the patient's medical history, as well as that of the entire family, hyperuricemia was discovered in his brother, while microscopic examination of his brother's and mother's urine revealed abundant uric acid crystals. After performing purine metabolic studies, it was determined that the two siblings suffered from partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency (Kelley-Seegmiller syndrome). This report highlights the importance of clinical awareness and a thorough examination of the patient's medical history for establishing an early diagnosis and commencing treatment for such rare inherited metabolic disorders to prevent renal failure.

"You can't make a monkey out of us": Galen and genetics versus Darwin.

The views on the biological relationship between human and ape are polarized. One end is summarized by the axiom that "man is the third chimpanzee", a thesis put forward in an indirect way initially by Charles Darwin in the 19th century. The other is a very modern concept that although similar, the human and ape genomes are distinctly different. We have compared these two views on the subject with the stance of the ancient medical writer Galen. There is a striking resemblance between current and ancient opinion on three key issues. Firstly, on the fact that man and apes are similar but not identical. Secondly, on the influence of such debates on fields much wider than biology. And finally, on the comparative usefulness of apes as a substitute for human anatomy and physiology studies.

Substitution of renal function through skin catharsis: evidence from the classical period to the Middle Ages.

The skin's cleansing capacity has been known for centuries and has been used therapeutically and extensively for a great number of diseases. We studied the historical evolution of the methods used for catharsis through the skin, particularly for those in renal failure, by reviewing most of the existing ancient Greek and Byzantine codices dealing with the skin's cleansing capacity. From the fragments cited in this article, it is evident that the ancient medical writers were well aware of the mechanism of perspiration, and through this process the excretion of several body toxins, they knew about renal failure as well as the influence of environmental temperature on blood purification via the skin. To validate their views, we reviewed the seasonal variation of the average values for blood urea, creatinine, and electrolytes for 161 regular dialysis treatment (RDT) patients in four dialysis units in southern Greece. The estimations were carried out during the winter/summer 1997, 1998, and 1999 terms and included three winter months and three summer months. We traced an unexpectedly large number of references in the ancient and medieval Greek medical literature concerning detoxification through the skin, mainly regarding patients in renal failure. This seasonal variation hypothesis is supported by the results of our retrospective study: there was a difference of 16 mg/dL in the average blood urea (mean winter urea 182 mg/dL, mean summer urea 166 mg/dL). We suggest that the ancients had a vivid idea about the substitution of renal function by the skin's cleansing ability in renal failure. The previously mentioned phenomenon may be due to the elimination of blood urea through excessive perspiration. Our clinical results seem to verify their notions, and hence, the skin (like the peritoneum) may be considered a natural membrane for dialysis. We were unable to trace a similar report in the literature on the seasonal fluctuation of blood urea in dialysis patients.

The human skin: a meeting ground for the ideas about macrocosm and microcosm in ancient and Medieval and Greek literature.

We have been interested in the cleansing capacity of skin during the recent years. In a paper of ours (1) we presented a few references to Hippocrates' and Galen's ideas on the subject, while the main body of the article was based on the 17th-20th centuries' relative practices. In a second paper (2), we were mainly testing the ancient and Medieval Greek ideas on skin catharsis against some clinical work of ours. In this paper we now present the ideas of the pagan and Byzantine Greek authors (5th cent. BC - 10th cent. AD) on the relationship of the human body to the natural and man-made world. Special emphasis is given to the relationship between purification through the skin and world purification. Based on the similarity of the Empedokles' concept of the four elements and Hippocrates' thesis concerning the four humours, the Earth itself was personified and became a living organism that felt cold, perspired and became dry. Man started to seek a natural explanation for his diseases and alterations of his body functions. Hence, perspiration, fever, urination, headache, stroke, were explained in cosmological terms. Extracts from many medical and non-medical writers, like Empedocles, Hippocrates, Aristotle, Galen, the Fathers of the Church, Meletius latrosophista, Theophilus Protospatharius, Michael Psellus and other sources are presented, in order to show the close relationship between an abundance of diseases and an array of natural phenomena.

Nephrology, a newly rich speciality, is looking for an illustrious ancestry: what about a famous grandfather?

Nephrology is a newborn speciality compared to the other medical specialities. However, the study of the urinary tract's physiology and pathology had begun simultaneously with the birth of medicine. The scientific revolution of the renaissance and enlightenment eras caused an intense contestation of earlier theories and methods as if all knowledge had evolved suddenly from parthenogenesis after the dark (?) medieval years and human intellect suddenly exploded to huge intelligence quotients after the 15th century while before that humans were mentally deprived. Indeed most of the scientific knowledge did evolve impressively during renaissance and enlightenment years but not through parthenogenesis. Some observations, discoveries and inventions of this era were actually reobservations, rediscoveries and reinventions. Such an example is that of the experiments of Sanctorius Santorii of the 16th century AD and of Erasistratus of the 3rd century BC. Sanctorius and Erasistratus carried out an experiment with the same basic principles, similar methodology and proportional results with an almost 2000 years lag phase. With our paper we wish to give credit to earlier researchers of physiological and medical knowledge who, despite the lack of technological support, often concluded in extremely accurate observations.

Ultraviolet inactivation of the infective agent of Aleutian disease of mink.

An experiment carried out to examine the effect of ultraviolet light on the aleutian disease agent in serum indicated that the agent was sensitive to irradiation.