Mortality from grossly encrusted bilateral pyelitis,ureteritis, and cystitis by Corynebacterium group D2

This is the first report of death due to gross encrustations of the entire upper urinary tract and bladder by Corynebacterium group D2 in a man with no history of renal transplantation or prolonged catheterizations. This case demonstrates that debilitated patients with a prior endoscopic procedure are at risk for this disease process. Prolonged treatment with appropriate antibiotics, acidification of the urine, and removal of crusts is essential for proper management.     

Cross talk between the renin-angiotensin-aldosterone system and vitamin D-FGF-23-klotho in chronic kidney disease

There is increasingly evidence that the interactions between vitamin D, fibroblast growth factor 23 (FGF-23), and klotho form an endocrine axis for calcium and phosphate metabolism, and derangement of this axis contributes to the progression of renal disease. Several recent studies also demonstrate negative regulation of the renin gene by vitamin D. In chronic kidney disease (CKD), low levels of calcitriol, due to the loss of 1-alpha hydroxylase, increase renal renin production. Activation of the renin-angiotensin-aldosterone system (RAAS), in turn, reduces renal expression of klotho, a crucial factor for proper FGF-23 signaling. The resulting high FGF-23 levels suppress 1-alpha hydroxylase, further lowering calcitriol. This feedback loop results in vitamin D deficiency, RAAS activation, high FGF-23 levels, and renal klotho deficiency, all of which associate with progression of renal damage. Here we examine current evidence for an interaction between the RAAS and the vitamin D-FGF-23-klotho axis as well as its possible implications for progression of CKD.     

Acute renal failure caused by Klebsiella pneumoniae pyelonephritis.

We report a 34-year-old male patient without prior medical history who presented with acute renal failure due to acute bacterial pyelonephritis. Both blood and urine cultures grew Klebsiella pneumoniae. Although a kidney biopsy revealed extensive necrosis and no viable glomeruli, renal function recovered to near normal after intermittent hemodialysis and antibiotic therapy. We believe that it is important to include this entity in the differential diagnosis of acute renal failure since proper diagnosis and treatment is essential for recovery of renal function. Furthermore, we would like to draw attention to Klebsiella pneumoniae as an important potential pathogen in such cases, in addition to Escherichia coli.     

Molecular regulation of phosphate metabolism by fibroblast growth factor-23-klotho system

Phosphorus is an essential nutrient and is routinely assimilated through consumption of food. The body's need of phosphate is usually fulfilled by intestinal absorption of this element from the consumed food, whereas its serum level is tightly regulated by renal excretion or reabsorption. Sodium-dependent phosphate transporters, located in the luminal side of the proximal tubular epithelial cells, have a molecular control on renal phosphate excretion and reabsorption. The systemic regulation of phosphate metabolism is a complex multiorgan process, and the identification of fibroblast growth factor-23 (FGF23)-Klotho system as a potent phosphatonin has provided new mechanistic insights into the homeostatic control of phosphate. Hypophosphatemia as a result of an increase in urinary phosphate wasting after activation of the FGF23-Klotho system is a common phenomenon, observed in both animal and human studies, whereas suppression of the FGF23-Klotho system leads to the development of hyperphosphatemia. This article will briefly summarize how delicate interactions of the FGF23-klotho system can regulate systemic phosphate homeostasis.     

Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies

Leukocyte trafficking from peripheral blood into affected tissues is an essential component of the inflammatory reaction to virtually all forms of injury and is an important factor in the development of many kidney diseases. Advances in the past few years have highlighted the central role of a family of chemotactic cytokines called chemokines in this process. Chemokines help to control the selective migration and activation of inflammatory cells into injured renal tissue. Chemokines and their receptors are expressed by intrinsic renal cells as well as by infiltrating cells during renal inflammation. This study summarizes the in vitro and in vivo data on chemokines and chemokine receptors in renal diseases with a special focus on potential therapeutic effects on inflammatory processes.     

Autosomal dominant polycystic kidney disease--clinical challenges

While not very common, the clinical anesthesiologist can expect to see between two and three patients per year with autosomal dominant polycystic kidney disease, ADPKD. Careful education and proper planning are essential to assure appropriate care for these patients. In addition, co-morbid conditions associated with the disease, make it especially challenging for the anesthesiologist who must be prepared for all contingencies. Also, decreased renal function and the systemic effects combine to create unique problems in properly anesthetizing these patients. Finally, proper preoperative assessment is essential to protect patients with ADPKD, and special care should be taken to select drugs that rely on non-renal metabolism for excretion. This review summarizes anesthetic considerations regarding epidemiologic, diagnostic, genetic, and perioperative clinical issues related to this disease.     

Dynamic (re)organization of the podocyte actin cytoskeleton in the nephrotic syndrome

The visceral glomerular epithelial cell, also known as the podocyte, plays an important role in the maintenance of renal glomerular function. This cell type is highly specialized and its foot processes together with the interposed slit diaphragm (SD) form the final barrier to urinary protein loss. Effacement of foot processes is associated with the development of proteinuria and—if not reversed in a certain time—with permanent deterioration of the glomerular filter. To maintain an intact glomerular filter barrier, podocyte-podocyte interactions and podocyte interactions with the glomerular basement membrane (GBM) are essential. Recent years have highlighted podocyte functions by unraveling the molecular composition of the SD, but have also clarified the important role of the podocyte actin cytoskeleton, and the podocyte-GBM interaction in the development of foot process (FP) effacement. This review provides an update of podocyte functions with respect to novel podocyte-specific proteins and also focuses on the dynamic interaction between the actin cytoskeleton of podocytes, their cell surface receptors and the GBM.     

Renal vein renin: value and limitations in the prediction of operative results.

Renal vein renin determinations, in contrast to isolated peripheral venous renin determinations, provide great help in the selection of patients who can benefit from an operation for renal hypertension. Patients with essential hypertension usually have renal vein renin ratios, larger/smaller, close to unity, but the available cumulative data show that, statistically, ratios as large as 2.0 may occur in this group (95 per cent confidence limits). In patients with unilateral stenosis of a main renal artery, large renal vein renin ratios (stenotic/normal) have been followed by operative success in more than 90 per cent of patients. However, many operative successes have also been achieved in patients without a large renal vein renin ratio. This may be explained by inaccurate renal vein catheterization, inactive renin secretion, nonsimultaneous sampling, assay variability, and problems related to bilateral or segmental lesions. Recent refinements in the interpretation of renal vein renin data (contralateral suppression, ipsilateral hypersecretion in absolute terms, and a combination analysis scoring system) appear to increase the accuracy of the test. Detailed anatomic information, provided by arteriography, is essential for proper interpretation of renal vein renin data.     

Molecular determinants for apical expression and regulatory membrane retrieval of the type IIa Na/Pi cotransporter

Renal inorganic phosphate (Pi) reabsorption is a key process in Pi homeostasis. Type IIa Na/Pi cotransporters, located at the apical membrane of renal proximal tubular cells, guarantee the vectorial transport of Pi. Renal Pi reabsorption can be modulated by controlling the number of cotransporters expressed at the apical membrane. Indeed, factors that increase Pi reabsorption induce the expression of type IIa cotransporters at the apical membrane, whereas factors that decrease Pi reabsorption lead to their retrieval. Therefore, proper sorting of this type of cotransporters is an essential step in Pi homeostasis. The relevance of polarization has been highlighted by the finding that improper sorting of transporters can cause disease. Here we describe the identification of signals involved in apical expression of newly synthesized type IIa cotransporters and in their hormonal-induced endocytosis.     

Development of the renal interstitium

 The kidney is derived from two tissue sources and develops through a series of mesenchymal-epithelial transitions and epithelial-mesenchymal interactions to form an epithelial tubular organ embedded in an interstitium derived from mesenchyme. The primary interstitium of the embryonic kidney undergoes significant differentiation to form the adult counterpart whose diverse cells have structural and functional characteristics that relate to their local milieu. Whether the adult interstitial cells retain the capacity to transform to other cell types and thus play a role in pathophysiological conditions appears more and more likely as the plasticity of cells becomes apparent. Besides forming the adult interstitium, the primary interstitium is active in metanephric development, with specific roles in nephron growth and collecting duct growth and arborization. Interruptions to the development of the interstitium or amelioration of its developmental capacity result in severely disrupted kidneys. The development of the renal interstitium is an essential component in the process of renal genesis. Received: 18 May 1998 / Revised: 25 August 1998 / Accepted: 31 August 1998     

The Macrophage Mediates the Renoprotective Effects of Endotoxin Preconditioning

Preconditioning is a preventative approach, whereby minimized insults generate protection against subsequent larger exposures to the same or even different insults. In immune cells, endotoxin preconditioning downregulates the inflammatory response and yet, preserves the ability to contain infections. However, the protective mechanisms of preconditioning at the tissue level in organs such as the kidney remain poorly understood. Here, we show that endotoxin preconditioning confers renal epithelial protection in various models of sepsis in vivo. We also tested the hypothesis that this protection results from direct interactions between the preconditioning dose of endotoxin and the renal tubules. This hypothesis is on the basis of our previous findings that endotoxin toxicity to nonpreconditioned renal tubules was direct and independent of immune cells. Notably, we found that tubular protection after preconditioning has an absolute requirement for CD14-expressing myeloid cells and particularly, macrophages. Additionally, an intact macrophage CD14-TRIF signaling pathway was essential for tubular protection. The preconditioned state was characterized by increased macrophage number and trafficking within the kidney as well as clustering of macrophages around S1 proximal tubules. These macrophages exhibited increased M2 polarization and upregulation of redox and iron-handling molecules. In renal tubules, preconditioning prevented peroxisomal damage and abolished oxidative stress and injury to S2 and S3 tubules. In summary, these data suggest that macrophages are essential mediators of endotoxin preconditioning and required for renal tissue protection. Preconditioning is, therefore, an attractive model to investigate novel protective pathways for the prevention and treatment of sepsis.     

Percutaneous renal biopsy

Percutaneous renal biopsy (PRB) is an integral part of the clinical practice of nephrology. It is essential in the diagnosis of glomerular, vascular, and tubulointerstitial diseases of the kidney, providing information that is invaluable in prognosis and patient management. The use of real-time ultrasound and automated biopsy needles has simplified and improved the success and safety of this procedure. In the recent past, we have seen a shift of the PRB from nephrologists to radiologists and this has raised appropriate concern that loss of this procedure may undermine the nephrologist's status as a subspecialist. We must continue to properly train young nephrologists in the proper technique and value of performing renal biopsy procedures or we stand to lose control of a procedure that was an integral part of the development of our subspecialty.     

Can angiography stage renal carcinoma?

We have compared the staging of renal carcinomas in 36 patients as judged preoperatively by angiography (T stage) and postoperatively by histopathology (P stage). Using the standard abdominal aortogram and selective renal arteriogram we found a considerable error rate in T staging (40%). The commonest error was preoperative overstaging, and this is probably determined by the behaviour of renal carcinoma, rather than by inadequate angiography. We conclude that whilst renal arteriography remains a useful diagnostic aid, it cannot answer questions on tumour extent with any accuracy. Staging by histopathology is essential for proper assessment and management of these patients.     

Congenital renal anomaly: evaluation with 99mTc-dimercaptosuccinic acid renal scintigraphy

Technetium 99m-2,3, dimercaptosuccinic acid (99mTc-DMSA) preferentially accumulates in the renal cortex, demonstrating functioning cortical mass. We used 99mTc-DMSA renal scintigraphy in ten patients with horseshoe kidneys and five patients with unilateral fused kidneys. The results show that 99mTc-DMSA renal scintigraphy reliably establishes the diagnosis of horseshoe kidney and clearly shows the isthmus, which is very essential for proper management. The technique also aids in the definitive assessment of separate kidney function and of total radionuclide uptake is possible using 99mTc-DMSA scintigraphy.     

Plasticity of kidney cells: role in kidney remodeling and scarring

The progression of renal scarring and the associated loss of function remains one of the main challenges in nephrology. Until recently, the glomerular and tubulointerstitial scarring processes were thought to involve primarily interactions between infiltrating inflammatory cells and resident renal cells culminating in loss of renal cells and their replacement by extracellular collagenous matrix (ECM). This review focuses on new aspects of renal response to injury and remodeling. Emphasis is on the plasticity of renal cells with the capacity of both glomerular and tubular cells to assume a range of phenotypes during the remodeling process. Both glomerular and tubular epithelial cells regress to primitive/embryonic mesenchymal phenotype in response to injury. This reverse embryogenesis is a key step in renal healing and scarring. In addition to the plasticity of intrinsic renal cells, it is becoming apparent that renal remodeling in health and disease involves the migration of progenitor hematopoietic stem cells into the kidneys. These cells assume various glomerular and tubular epithelial phenotype. They are also involved in the evolution of lesions toward healing or scarring. A better understanding of some of these key events in renal remodeling and their mediators may open the way to new interventions based on their manipulations and aimed at favoring renal healing and preventing scarring.     

Renal remodelling: complex interactions between renal and extra-renal cells

An increasing number of patients suffer from chronic kidney disease (CKD). The progression of CKD is often relentless with the majority of patients reaching end-stage renal disease (ESRD) requiring dialysis. Such a progression depends on complex renal pathology leading to fibrosis. The understanding of the pathophysiology of progressive renal remodelling and scarring has highlighted different pathways based on interactions between intrinsic and extrinsic renal cells. This review discusses the contribution of extrinsic haematopoietic cells to the remodelling that follows a renal insult. It highlights the involvement of bone marrow-derived stem cells in the remodelling of glomerular as well as tubulo-interstitial cells. It also points to the capacity of the kidney cells to dedifferentiate into embryonic phenotypes thus allowing them an active contribution to renal tissue regeneration.     

Renal abscesses: Classification and review of 40 cases

Renal abscesses are misdiagnosed often and, consequently, mistreated or treated too late. Forty cases of renal abscesses divided into anatomic categories — perinephric, renal cortical, and corticomedullary — are reviewed. Various conditions seem to predispose to renal abscesses: urinary tract infections, vesicoureteral reflux, calculi, or other medical problems. This retrospective study discloses that a high correlation exists between organisms found in the patients' urine cultures and those organisms cultured from all 3 categories of abscesses. Accurate and complete urine bacteriologic study is therefore an essential tool for diagnosis.     

Pathophysiology of renal function and its effect on isotope studies in the workup of hydronephrosis

Understanding renal maturation and growth is essential before adequate interpretation of radionuclide renal studies can be done. The expectation that an immature kidney draining into a dilated renal pelvis will show good washout on a diuretic renogram within 20 or 40 min is unreasonable. A physiological explanation for this is given.