Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes Thus, despite the fact that all fish groups have functional kidneys, the gill epithelium is the site of many processes that are mediated by renal epithelia in terrestrial vertebrates Indeed, many of the pathways that mediate these processes in mammalian renal epithelial are expressed in the gill, and many of the extrinsic and intrinsic modulators of these processes are also found in fish endocrine tissues and the gill itself The basic patterns of gill physiology were outlined over a half century ago, but modern immunological and molecular techniques are bringing new insights into this complicated system Nevertheless, substantial questions about the evolution of these mechanisms and control remain

https://people.clas.ufl.edu/devans/files/PRVGill.pdf

The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste

KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Section I: Anatomy Surgical Anatomy of the Retroperitoneum, Kidneys, and Ureters Anatomy of the Lower Urinary Tract and Male Genitalia Section II: Clinical Decision Making Evaluation of the Urologic Patient: History, Physical Examination, and Urinalysis Urinary Tract Imaging: Basic Principles Outcomes Research Section III: Basics of Urologic Surgery Basic Instrumentation and Cystoscopy Basics of Laparoscopic Urologic Surgery Section IV: Infections and Inflammation Infections of the Urinary Tract-A. Schaeffer Inflammatory Conditions of the Male Genitourinary Tract Interstitial Cystitis and Related Disorders Sexually Transmitted and Associated Diseases Urological Implications of AIDS and Related Conditions Cutaneous Diseases of the External Genitalia Tuberculosis and Other Opportunistic Infections of the Genitourinary System Section V: Molecular and Cellular Biology Basic Principles of Immunology Molecular Genetics and Cancer Biology Tissue Engineering Perspectives for Reconstructive Surgery Section VI: Reproductive and Sexual Function Male Reproductive Physiology Male Infertility Surgical Management of Male Infertility Physiology of Erectile Dysfunction: Pathophysiology, Evaluation, Nonsurgical Management Epidemiology, Evaluation, and Nonsurgical Management of Erectile Dysfunction Prosthetic Surgery for Erectile Dysfunction Vascular Surgery for Erectile Dysfunction Peyronie's Disease Priapism Androgen Deficiency in the Aging Male Female Sexual Function and Dysfunction Section VII: Male Genitalia Neoplasms of the Testis Surgery of Testicular Tumors Tumors of the Penis Surgery of Penile and Urethral Carcinoma Surgery of the Penis and Urethra Surgery of the Scrotum and Seminal Vesicles Section VIII: Renal Physiology and Pathophysiology Renal Physiology and Pathophysiology Renovascular Hypertension Section IX: Upper Urinary Tract Obstruction and Trauma Pathophysiology of Obstruction Management of Upper Urinary Tract Obstruction Upper Urinary Tract Trauma Section X: Renal Failure and Transplantation Renal Transplantation Etiology, Pathogenesis, and Management of Renal Failure Section XI: Urinary Lithiasis and Endourology Urinary Lithiasis: Etiology, Epidemiology, and Pathophysiology Evaluation and Medical Management of Urinary Lithiasis Surgical Management of Upper Urinary Tract Calculi Ureteroscopy and Retrograde Ureteral Access Percutaneous Approaches to the Upper Urinary Tract Section XII: Neoplasms of the Upper Urinary Tract Renal Tumors Urothelial Tumors of the Upper Urinary Tract Urothelial Tumors of the Renal Pelvis and Ureter Open Surgery of the Kidney Laparoscopic Surgery of the Kidney Ablative Therapy for Renal Tumors Section XIII: The Adrenals Pathophysiology, Evaluation, and Medical Management of Adrenal Disorders Surgery of the Adrenals Section XIV: Urine Transport, Storage, and Emptying Physiology and Pharmacology of the Renal Pelvis and Ureter Physiology and Pharmacology of the Bladder and Urethra Pathophysiology, Categorization, and Management of Voiding Dysfunction Urodynamic and Video dynamic Evaluation of Voiding Dysfunction Neuromuscular Dysfunction of the Lower Urinary Tract Urinary Incontinence: Epidemiology, Pathophysiology, Evaluation, and Overview of Management The Overactive Bladder Pharmacologic Management of Storage and Emptying Failure Conservative Management of Urinary Incontinence: Behavioral and Pelvic Floor Therapy, Urethral and Pelvic Devices Electrical Stimulation and Neuromodulation in Storage and Emptying Failure Retropubic Suspension Surgery for Incontinence in Women Vaginal Reconstructive Surgery for Sphincteric Incontinence Pubovaginal Slings Tension-Free Vaginal Tape Procedures Injection Therapy for Urinary Incontinence Additional Treatment for Storage and Emptying Failure Geriatric Voiding Dysfunction and Urinary Incontinence Urinary Tract Fistulae Bladder and Urethral Diverticula Surgical Procedures for Sphincteric Incontinence in the Male: The Artificial Genitourinary Sphincter Perineal Sling Procedures Section XV: Bladder Lower Genitourinary Calculi and Trauma Urothelial Tumors of the Bladder Management of Superficial Bladder Cancer Management of Metastatic and Invasive Bladder Cancer Surgery of Bladder Cancer Laparoscopic Bladder Surgery Use of Intestinal Segments in Urinary Diversion Cutaneous Continent Urinary Diversion Orthotopic Urinary Diversion Genital and Lower Urinary Tract Trauma Lower Urinary Tract Calculi Section XVI: Prostate Molecular Biology, Endocrinology, and Physiology of the Prostate and Seminal Vesicles Etiology, Pathophysiology, and Epidemiology of Benign Prostatic Hyperplasia Natural History, Evaluation, and Nonsurgical Management of Benign Prostatic Hyperplasia Minimally Invasive and Endoscopic Management of Benign Prostatic Hyperplasia Retropubic and Superpubic Open Radical Prostatectomy Epidemiology, Etiology, and Prevention of Prostate Cancer Pathology of Prostatic Neoplasms Ultrasonography and Biopsy of the Prostate Tumor Markers in Prostate Cancer Early Detection, Diagnosis, and Staging of Prostate Cancer Definitive Therapy of Localized Prostate Cancer: Outcomes Expectant Management of Prostate Cancer Anatomic Retrograde Retropubic Prostatectomy Radical Perineal Prostatectomy Laparoscopic and Robotic Radical Prostatectomy and Pelvic Lymphadenectomy Radiation Therapy for Prostate Cancer Cryotherapy of Prostate Cancer Treatment of Locally Advanced Prostate Cancer Management of Rising Prostate-Specific Antigen after Definitive Therapy Hormonal Therapy for Prostate Cancer Management of Hormone-Resistant Prostate Cancer Section XVII: Pediatric Urology Normal and Anomalous Development of the Urinary Tract Renal Function in the Fetus Congenital Obstructive Uropathy Perinatal Urology Evaluation of Pediatric Urologic Patient Renal Disease in Childhood Urinary Tract Infections in Infants and Children Anomalies of the Kidney Renal Dysplasia and Cystic Disease of Kidney Anomalies and Surgery of the Ureteropelvic Junction Ectopic Ureter Vesicoureteral Reflux Prune-Belly Syndrome Exstrophy and Epispadias Complex Surgical Technique for One-Stage Exstrophy Reconstruction Bladder Anomalies in Children Posterior Urethral Valves and Other Urethral Anomalies Voiding Dysfunction in Children: Neurogenic and Non-neurogenic Urinary Tract Reconstruction Hypospadias Abnormalities of External Genitalia in Boys Abnormalities of Testis and Scrotum: Surgical Management Sexual Differentiation: Normal and Abnormal Surgical Management of Intersex Pediatric Oncology Pediatric Endourology and Laparoscopy Pediatric Genitourinary Trauma

Campbell-Walsh urology

The use of the calcineurin inhibitors cyclosporine and tacrolimus led to major advances in the field of transplantation, with excellent short-term outcome. However, the chronic nephrotoxicity of these drugs is the Achilles' heel of current immunosuppressive regimens. In this review, the authors summarize the clinical features and histologic appearance of both acute and chronic calcineurin inhibitor nephrotoxicity in renal and nonrenal transplantation, together with the pitfalls in its diagnosis. The authors also review the available literature on the physiologic and molecular mechanisms underlying acute and chronic calcineurin inhibitor nephrotoxicity, and demonstrate that its development is related to both reversible alterations and irreversible damage to all compartments of the kidneys, including glomeruli, arterioles, and tubulo-interstitium. The main question--whether nephrotoxicity is secondary to the actions of cyclosporine and tacrolimus on the calcineurin-NFAT pathway--remains largely unanswered. The authors critically review the current evidence relating systemic blood levels of cyclosporine and tacrolimus to calcineurin inhibitor nephrotoxicity, and summarize the data suggesting that local exposure to cyclosporine or tacrolimus could be more important than systemic exposure. Finally, other local susceptibility factors for calcineurin inhibitor nephrotoxicity are reviewed, including variability in P-glycoprotein and CYP3A4/5 expression or activity, older kidney age, salt depletion, the use of nonsteroidal anti-inflammatory drugs, and genetic polymorphisms in genes like TGF-beta and ACE. Better insight into the mechanisms underlying calcineurin inhibitor nephrotoxicity might pave the way toward more targeted therapy or prevention of calcineurin inhibitor nephrotoxicity.

Calcineurin Inhibitor Nephrotoxicity

About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics.

Kidney stone disease

Our purpose here is to test the hypothesis that Randall’s plaques, calcium phosphate deposits in kidneys of patients with calcium renal stones, arise in unique anatomical regions of the kidney, their formation conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative biopsies of plaques in kidneys of idiopathic-calcium-stone formers and patients with stones due to obesity-related bypass procedures and obtained papillary specimens from non–stone formers after nephrectomy. Plaque originates in the basement membranes of the thin loops of Henle and spreads from there through the interstitium to beneath the urothelium. Patients who have undergone bypass surgery do not produce such plaque but instead form intratubular hydroxyapatite crystals in collecting ducts. Non–stone formers also do not form plaque. Plaque is specific to certain kinds of stone-forming patients and is initiated specifically in thin-limb basement membranes by mechanisms that remain to be elucidated.

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Randall’s plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle

Dose-related cyclosporine-induced renal dysfunction is the most frequent adverse effect noted with this exciting immunosuppressive drug. To investigate pathogenetic factors involved, we studied renal tubular function and afferent arteriolar morphology during severe experimental cyclosporine-induced reduction in glomerular filtration rate. Pair-fed male rats were given cyclosporine 50 mg/kg or olive oil vehicle alone by gavage for periods of 3-14 days. Glomerular filtration rate declined progressively, reaching a nadir of 0.18 +/- .05 ml/min/100 g vs. .86 +/- .03 ml/min/100 g in controls at 14 days (P less than 0.001). Despite the severe reduction in glomerular filtration rate there was no difference in fractional sodium excretion, fractional lithium excretion, enzymuria, or in vitro renal cortical slice uptake of tetraethylammonium in cyclosporine and vehicle-treated animals. Light microscopy showed vacuolar changes without evidence of tubular necrosis at 7 and 14 days in cyclosporine-treated rats. Progressive decline in the diameter of the afferent arteriole was noted by scanning electron microscopy. By day 14 the lumenal diameter of afferent arterioles from cyclosporine-treated animals was 8.9 +/- 0.4 micron vs. 13.5 +/- 0.4 micron in controls (P less than 0.05). We conclude that afferent arteriolar vasoconstriction rather than direct tubular injury is a major pathogenetic factor in experimental cyclosporine nephrotoxicity.

Cyclosporine-induced acute renal dysfunction in the rat. Evidence of arteriolar vasoconstriction with preservation of tubular function.

Urolithiasis is one of the most common urologic diseases in industrialized societies. Calcium oxalate is the predominant component in 70–80% of kidney stones1, and small changes in urinary oxalate concentration affect the risk of stone formation2. SLC26A6 is an anion exchanger expressed on the apical membrane in many epithelial tissues, including kidney and intestine3,4,5,6. Among its transport activities, SLC26A6 mediates Cl−-oxalate exchange5,6,7,8,9. Here we show that mutant mice lacking Slc26a6 develop a high incidence of calcium oxalate urolithiasis. Slc26a6-null mice have significant hyperoxaluria and elevation in plasma oxalate concentration that is greatly attenuated by dietary oxalate restriction. In vitro flux studies indicated that mice lacking Slc26a6 have a defect in intestinal oxalate secretion resulting in enhanced net absorption of oxalate. We conclude that the anion exchanger SLC26A6 has a major constitutive role in limiting net intestinal absorption of oxalate, thereby preventing hyperoxaluria and calcium oxalate urolithiasis.

Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.

Biophysical and biological bases of stone formation clinical and laboratory evaluation of urolithiases surgical management of stones medical and surgical management of specific stone types struvite stones

Andrew P. Evan

Papers

Kidney stone disease

Randall’s plaque of patients with nephrolithiasis begins in basement membranes of thin loops of Henle

Cyclosporine-induced acute renal dysfunction in the rat. Evidence of arteriolar vasoconstriction with preservation of tubular function.

Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6.

Kidney stones : medical and surgical management