Renal co-morbidity in patients with rheumatic diseases

Renal co-morbidity is common in patients with rheumatic disease based on regular assessment of serum and urine parameters of renal function. When patients present with both arthritis and renal abnormalities the following questions have to be addressed. Is kidney disease a complication of rheumatic disease or its management, or are they both manifestations of a single systemic autoimmune disease? Is rheumatic disease a complication of kidney disease and its management? How do rheumatic disease and kidney disease affect each other even when they are unrelated? The present review provides an overview of how to address these questions in daily practice.     

Transmission of Pneumocystis infection in humans

Is Pneumocystis pneumonia (PcP) a transmissible fungal disease? Does nosocomial PcP occur? Is there Pneumocystis transmission in the community? These questions, which could not be tackled before the 2000s, may at present be approached using either noninvasive detection methods or experimental transmission models. Represented by a unique entity (P.?carinii) for almost one century, the Pneumocystis genus was shown to contain several species, being P.?jirovecii the sole species identified in humans hitherto. Molecular methods combined with cross infection experiments revealed strong host specificity that precludes Pneumocystis inter-species transmission. In contrast, respiratory transmission between mammals of a same species is usually highly active, even between immunocompetent hosts. Other transmission ways could also exist. New data show that human being is the unique P.?jirovecii reservoir; it would constitute the sole infection source in both hospital and community.     

Treatment of renal failure from diabetic nephropathy with cadaveric homograft

We report two patients with terminal renal failure secondary to diabetic nephropathy treated with cadaveric kidney transplantation. Neither of these patients had peripheral vascular disease or peripheral neuropathy. There was a proliferative diabetic retinopathy with hemorrhages and exudates in one patient and only background diabetic changes in the ocular fundi of the other; there have been no significant changes in visual acuity or retinopathy in either patient following the transplantation. Both have good kidney function after 8 and 15 months and are completely rehabilitated.The requirement for insulin decreased in both patients during the period of renal insufficiency and increased following transplantation; this seemed to be related to the large dose of steroids given because now that a maintenance level of steroids has been established, both patients require the same dosage of insulin as they did before the onset of renal insufficiency.     

RHEUMATIC FEVER IN COLLEGE STUDENTS

The results of three independent surveys concerned with rheumatic fever and heart disease in students at the University of California were assembled and found to be in close agreement. A full 2 per cent of all students believed they had had rheumatic fever; and several times that proportion gave a history of one of the rheumatic manifestations. Only 0.25 per cent had demonstrable rheumatic heart disease and 0.1 per cent had congenital heart disease.Physiologic murmurs may occur in 3 per cent or more of students entering college.Penicillin prophylaxis is important in persons with rheumatic heart disease, but it is important not to put a label of rheumatic heart disease on persons who think they have had rheumatic fever but who have no demonstrable heart disease. Long term penicillin prophylaxis or other long term prophylactic procedures directed against rheumatic fever are not indicated unless the diagnostic criteria for rheumatic fever are clearly met or unless rheumatic heart involvement is definitely present.     

Do nonribosomal peptide synthetases occur in higher eukaryotes?

Is There An Answer? is intended to serve as a forum in which readers to IUBMB Life may pose questions of the type that intrigue biochemists but for which there may be no obvious answer or one may be available but not widely known or easily accessible. Readers are invited to e-mail ascenzi@uniroma3.it if they have questions to contribute or if they can provide answers to questions that are provided here from time to time. In the latter case, instructions will be sent to interested readers. Answers should be, whenever possible, evidence-based and provide relevant references. Paolo Ascenzi     

Cholecystokinin and panic disorder--three unsettled questions

The serendipitously discovered panicogenic effect of the cholecystokinin fragment, the C-terminal tetrapeptide amide (CCK-4), has suggested that the widespread network of CCK neurons and corresponding CCK-B receptors in the brain are in some way involved in pathogenesis panic disorders in man. Two decades of research have now established that exogenous CCK-4 in a reproducible, dose-dependent and sensitive manner indeed evokes panic attacks in both healthy subjects and at even lower doses in anxiety patients. But several questions about the molecular mechanisms by which endogenous CCK peptides may precipitate panic attacks remain to be answered. This review focuses on three immediate questions. (1) Does endogenous CCK-4 exist? (2) Is the panicogenic effect mediated only through CCK-B receptors? (3) Are measurements of CCK peptides in cerebrospinal fluid of use in elucidating the pathogenesis and/or diagnosis? This review concludes that the answers to these questions may further the understanding of panic disorder substantially, and hence contribute to improved diagnosis and therapy of the disease.     

Is there a special conservation biology?

Conservation biology is special to the extent that it fills useful roles in the scientific and conservation fields that are not being filled by practitioners of other disciplines. The emergence of the “new conservation biology” in the late 1970's and its blossoming in the 1980's and 1990's reflect, to a large degree, a failure of traditional academic ecology and the natural resource disciplines to address modern conservation problems adequately. Yet, to be successful conservation biology, as an interdisciplinary field, must build on the strengths of other disciplines both basic and applied. The new conservation biology grew out of concern over extinction of species, although the field has expanded to include issues about management of several levels of biological organization. I examine four controversial questions of importance to conservation biologists today: 1) are there any robust principles of conservation biology? 2) Is advocacy an appropriate activity of conservation biologists? 3) Are we educating conservation biologists properly? 4) Is conservation biology distinct from other biological and resource management disciplines? I answer three of these questions with a tentative “yes” and one (3) with a regretful “in most cases, no.” I see a need for broader Training for students of conservation biology, more emphasis on collecting basic field data, compelling applications of conservation biology to real problems, increased influence on policy, and expansion of the international scope of the discipline. If all these occur, conservation biology will by truly special.     

The Kolff-Merrill artificial kidney; clinical application in acute renal insufficiency

Acute renal insufficiency is often called "lower nephron nephrosis." Its recognition, its prognostic significance, and its therapy by conservative measures are receiving increasing clinical emphasis. The mortality rate in this complicated syndrome still remains unduly high. One method of therapy of anuric patients whose lives are in jeopardy because of fulminating uremia or critical potassium intoxication is use of an artificial kidney to "purify" the blood stream by means of extracorporeal dialysis.The author describes clinical (and laboratory) experience with ten such dialyzed patients, eight of whom presented the classical picture of acute renal insufficiency. Four died, one from unrecognized coronary occlusion, another from antecedent, overwhelming peritonitis. Two other patients with chronic kidney disorders received no benefit from dialysis and died of renal disease. Good biochemical and clinical response was brought about in six cases of lower nephron nephrosis. Presumably, these six patients would have died had they not been subjected to artificial dialysis.     

Oral implants in dependent elderly persons: blessing or burden?

doi:10.1111/j.1741‐2358.2009.00314.x
Oral implants in dependent elderly persons: blessing or burden? Background: Implant‐supported (partial) dentures may raise problems in patients who have become dependent on others for daily oral health care. Dental hygienists and general dental practitioners, as well as care providers, volunteer aiders and even health care insurance companies, should anticipate the growing demand for specific oral health care for patients provided with implant‐supported (partial) dentures. Objective: To report three cases of dependent patients and to present recommendations to prevent or resolve implant‐related oral problems. Materials and methods: The three case reports are demonstrating that implant insertion in (dependent) elderly people needs careful consideration. Discussion: When considering implant treatment, some questions should be raised: (1) Is the treatment appropriate in contributing to the patient’s well‐being and quality of life? (2) Is the treatment the most suitable treatment? (3) Does the treatment integrate with the patient’s oral health care plan? (4) Is the patient sufficiently cooperative? (5) Is the patient supported by a well‐functioning oral (self) care assisting network? (6) Is it possible for the patient to regular see an oral health care professional and is oral health care easily accessible in cases of an emergency? Conclusion: Dependent elderly people can benefit from oral implants, providing that adequate oral health care and aftercare can be provided. When indicated, removal of the anchorage structure is easily performed by putting the implants to sleep. All implant patients should be provided with an ‘implant passport’. Regular information and instruction for care providers about the oral condition of the patient are essential.     

Emerging roles for lymphatics in acute kidney injury: Beneficial or maleficent?

Acute kidney injury, a sudden decline in renal filtration, is a surprisingly common pathology resulting from ischemic events, local or systemic infection, or drug-induced toxicity in the kidney. Unchecked, acute kidney injury can progress to renal failure and even recovered acute kidney injury patients are at an increased risk for developing future chronic kidney disease. The initial extent of inflammation, the specific immune response, and how well inflammation resolves are likely determinants in acute kidney injury-to-chronic kidney disease progression. Lymphatic vessels and their roles in fluid, solute, antigen, and immune cell transport make them likely to have a role in the acute kidney injury response. Lymphatics have proven to be an attractive target in regulating inflammation and immunomodulation in other pathologies: might these strategies be employed in acute kidney injury? Acute kidney injury studies have identified elevated levels of lymphangiogenic ligands following acute kidney injury, with an expansion of the lymphatics in several models post-injury. Manipulating the lymphatics in acute kidney injury, by augmenting or inhibiting their growth or through targeting lymphatic-immune interactions, has met with a range of positive, negative, and sometimes inconclusive results. This minireview briefly summarizes the findings of lymphatic changes and lymphatic roles in the inflammatory response in the kidney following acute kidney injury to discuss whether renal lymphatics are a beneficial, maleficent, or a passive contributor to acute kidney injury recovery.     

microRNAs in kidneys: biogenesis, regulation, and pathophysiological roles

MicroRNAs (miRNA) are endogenously produced, short RNAs that repress and thus regulate the expression of almost half of known protein-coding genes. miRNA-mediated gene repression is an important regulatory mechanism to modulate fundamental cellular processes such as the cell cycle, growth, proliferation, phenotype, and death, which in turn have major influences on pathophysiological outcomes. In kidneys, miRNAs are indispensable for renal development and homeostasis. Emerging evidence has further pinpointed the pathogenic roles played by miRNAs in major renal diseases, including diabetic nephropathy, acute kidney injury, renal carcinoma, polycystic kidney disease, and others. Although the field of renal miRNA research is still in its infancy and important questions remain, future investigation on miRNA regulation in kidneys has the potential to revolutionize both the diagnosis and treatment of major renal diseases.     

Phylogenetic analysis of the Malacostraca (Crustacea)

The Malacostraca comprises about 28 000 species with a broad disparity in morphology, anatomy, embryology, behaviour and ecology. The phylogenetic relationships of the major taxa are still under debate. Is the Leptostraca the sister group of the remaining Malacostraca, or is this taxon more closely related to other Crustacea? Does the Stomatopoda or the Bathynellacea represent the most basal taxon within the remaining taxa? Is the Peracarida monophyletic or are some peracarid taxa more closely related to other ‘caridoid’ taxa? Is the Thermosbaenacea part of the Peracarida or its sister group, and how much support is there for a taxon Amphipoda + Isopoda? To answer these questions a phylogenetic analysis of the Malacostraca combining different phylogenetic approaches was undertaken. In a first step, the monophyly of the Malacostraca including the Leptostraca is shown using the ‘Hennigian approach’. A computer cladistic analysis of the Malacostraca was carried out with NONA and PEE ‐WEE , based on 93 characters from morphology, anatomy and embryology. Nineteen higher malacostracan taxa are included in our analysis. Taxa whose representatives are exclusively fossils were not included. The Leptostraca was used as an operational out‐group. The present analysis supports the basal position of the Stomatopoda. Syncarida and Peracarida (including Thermosbaenacea) are supported as monophyletic, the Eucarida is not. Instead a sister‐group relationship is suggested between Euphausiacea and Peracarida (including Thermosbaenacea), with the Syncarida as the sister group to both taxa. Certain embryonic characters are interpreted as support for the monophyly of the Peracarida (without Thermosbaenacea) because convergences or reversals of these characters seem implausible. Within the Peracarida, the Mysidacea (Lophogastrida + Mysida) represents the sister group to the remaining taxa. A sister‐group relationship between Amphipoda and Isopoda is not supported.     

Four danger response programs determine glomerular and tubulointerstitial kidney pathology

Renal biopsies commonly display tissue remodeling with a combination of many different findings. In contrast to trauma, kidney remodeling largely results from intrinsic responses, but why? Distinct danger response programs were positively selected throughout evolution to survive traumatic injuries and to regenerate tissue defects. These are: (1) clotting to avoid major bleeding, (2) immunity to control infection, (3) epithelial repair and (4) mesenchymal repair. Collateral damages are acceptable for the sake of host survival but causes for kidney injury commonly affect the kidneys in a diffuse manner. This way, coagulation, inflammation, deregulated epithelial healing or fibrosis contribute to kidney remodeling. Here, I focus on how these ancient danger response programs determine renal pathology mainly because they develop in a deregulated manner, either as insufficient or overshooting processes that modulate each other. From a therapeutic point of view, immunopathology can be prevented by suppressing sterile renal inflammation, a useless atavism with devastating consequences. In addition, it appears as an important goal for the future to promote podocyte and tubular epithelial cell repair, potentially by stimulating the differentiation of their newly discovered intrarenal progenitor cells. By contrast, it is still unclear whether selectively targeting renal fibrogenesis can preserve or bring back lost renal parenchyma, which would be required to maintain or improve kidney function. Thus, renal pathology results from ancient danger responses that evolved because of their evolutional benefits upon trauma. Understanding these causalities may help to shape the search for novel treatments for kidney disease patients.     

Four danger response programs determine glomerular and tubulointerstitial kidney pathology: Clotting, inflammation, epithelial and mesenchymal healing

Renal biopsies commonly display tissue remodeling with a combination of many different findings. In contrast to trauma, kidney remodeling largely results from intrinsic responses, but why? Distinct danger response programs were positively selected throughout evolution to survive traumatic injuries and to regenerate tissue defects. These are: (1) clotting to avoid major bleeding, (2) immunity to control infection, (3) epithelial repair and (4) mesenchymal repair. Collateral damages are acceptable for the sake of host survival but causes for kidney injury commonly affect the kidneys in a diffuse manner. This way, coagulation, inflammation, deregulated epithelial healing or fibrosis contribute to kidney remodeling. Here, I focus on how these ancient danger response programs determine renal pathology mainly because they develop in a deregulated manner, either as insufficient or overshooting processes that modulate each other. From a therapeutic point of view, immunopathology can be prevented by suppressing sterile renal inflammation, a useless atavism with devastating consequences. In addition, it appears as an important goal for the future to promote podocyte and tubular epithelial cell repair, potentially by stimulating the differentiation of their newly discovered intrarenal progenitor cells. By contrast, it is still unclear whether selectively targeting renal fibrogenesis can preserve or bring back lost renal parenchyma, which would be required to maintain or improve kidney function. Thus, renal pathology results from ancient danger responses that evolved because of their evolutional benefits upon trauma. Understanding these causalities may help to shape the search for novel treatments for kidney disease patients.     

Applying Weight-of-Evidence in Retrospective Ecological Risk Assessment When Quantitative Data Are Limited

Retrospective ecological risk assessment attempts to identify likely causal agents to explain adverse effects that have occurred in ecological targets. It can never be decisive since it is post hoc and usually based on limited evidence that is rarely very quantitative. It can, nevertheless, be made more transparent, systematic, and logical, and less subjective. Based on human health epidemiological criteria we develop an approach that moves from systematic consideration of seven basic questions to assigning a likelihood of involvement of putative agents. The questions are: 1. Is there evidence that the target is or has been exposed to the agent? 2. Is there evidence for correlation between adverse effects in the target and exposure to the agent either in time or in space? 3. Do the measured or predicted environmental concentrations exceed quality criteria for water, sediment or body burden? 4. Have the results from controlled experiments in the field or laboratory led to the same effect? 5. Has removal of the agent led to amelioration of effects in the target? 6. Is there an effect in the target known to be specifically caused by exposure to the agent? 7. Does the proposed causal relationship make sense logically and scientifically? We identify 15 common scenarios of answers to the questions and illustrate the approach by reference to three real-world case studies (decline in benthos in a tropical marine bay, decline in fisheries in a temperate sea, decline in marine mollusc populations). The primary challenge in retrospective risk assessment is to make best use of the available evidence to develop rational management strategies and/or guide additional analyses to gain further evidence about likely agents as causes of observed harm.     

A systematic review on nephron protective AYUSH drugs as constituents of NEERI-KFT (A traditional Indian polyherbal formulation) for the management of chronic kidney disease

Chronic Kidney Disease (CKD) is a major health problem characterized by kidney dysfunction with progressive segmental glomerulosclerosis to end-stage renal disease (ESRD). Due to lack of scientific data and comprehensive reports, the current systematic review provides an inclusive understanding and prospective associated with phytopharmacology of NEERI-KFT in CKD. The data was collected from more than five databases such as Science Direct, Google Scholar, Elsevier, PubMed, Springer, ACS publication etc using keywords like CKD/Kidney disease, epidemiology/prevalence, modern therapies for CKD management, NEERI-KFT and its role in kidney disease. The study was performed based on scientific reports screened by experts according to inclusion and exclusion criteria. The pre-clinical and clinical findings suggested that NEERI-KFT has promising effects as nephroprotective and considered safe and well effective in primary care of kidney against disease. Phytopharmacological evaluation of NEERI-KFT suggest that it exhibit substantial potential against oxidative and inflammatory stress induced apoptosis by exerting antioxidants, nephroprotective and immunomodulatory effects. Hence, it can be enlighten that NEERI-KFT have potential herbs which exerts significant antioxidants, nephroprotective and immunomodulatory effects in the patients associated with renal dysfunction or CKD thus improving altered renal architecture and renal physiology. Clinically, it is concluded that NEERI-KFT works kidney malfunction and cease ESRD progression or even reduce the number of dialysis.     

Ideas about control of skeletal and cardiac muscle blood flow (1876-2003): cycles of revision and new vision.

This perspective examines origins of some key ideas central to major issues to be addressed in five subsequent mini-reviews related to Skeletal and Cardiac Muscle Blood Flow. The questions discussed are as follows. 1). What causes vasodilation in skeletal and cardiac muscle and 2). might the mechanisms be the same in both? 3). How important is muscle's mechanical contribution (via muscle pumping) to muscle blood flow, including its effect on cardiac output? 4). Is neural (vasoconstrictor) control of muscle vascular conductance and muscle blood flow significantly blunted in exercise by muscle metabolites and what might be a dominant site of action? 5). What reflexes initiate neural control of muscle vascular conductance so as to maintain arterial pressure at its baroreflex operating point during dynamic exercise, or is muscle blood flow regulated so as to prevent accumulation of metabolites and an ensuing muscle chemoreflex or both?     

Habitat fragmentation: A long and tangled tale

In this essay: I provide a brief history of habitat fragmentation research; I describe why its “non‐questions” (‘Is habitat fragmentation a big problem for wildlife species?” and, “Are the effects of habitat fragmentation generally negative or positive?”) are important to conservation; I outline my role in tackling these questions; I discuss reasons why the culture of habitat fragmentation research is largely incapable of accepting the answers; and I speculate on the future of habitat fragmentation research.     

Sarcoidosis in Native and Transplanted Kidneys: Incidence,Pathologic Findings,and Clinical Course

Renal involvement by sarcoidosis in native and transplanted kidneys classically presents as non caseating granulomatous interstitial nephritis. However, the incidence of sarcoidosis in native and transplant kidney biopsies, its frequency as a cause of end stage renal disease and its recurrence in renal allograft are not well defined, which prompted this study. The electronic medical records and the pathology findings in native and transplant kidney biopsies reviewed at the Johns Hopkins Hospital from 1/1/2000 to 6/30/2011 were searched. A total of 51 patients with a diagnosis of sarcoidosis and renal abnormalities requiring a native kidney biopsy were identified. Granulomatous interstitial nephritis, consistent with renal sarcoidosis was identified in kidney biopsies from 19 of these subjects (37%). This is equivalent to a frequency of 0.18% of this diagnosis in a total of 10,023 biopsies from native kidney reviewed at our institution. Follow-up information was available in 10 patients with biopsy-proven renal sarcoidosis: 6 responded to treatment with prednisone, one progressed to end stage renal disease. Renal sarcoidosis was the primary cause of end stage renal disease in only 2 out of 2,331 transplants performed. Only one biopsy-proven recurrence of sarcoidosis granulomatous interstitial nephritis was identified.

Conclusions

Renal involvement by sarcoidosis in the form of granulomatous interstitial nephritis was a rare finding in biopsies from native kidneys reviewed at our center, and was found to be a rare cause of end stage renal disease. However, our observations indicate that recurrence of sarcoid granulomatous inflammation may occur in the transplanted kidney of patients with sarcoidosis as the original kidney disease.