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Objective The objective of this study is to compare the outcomes of hospital mortality, the requirement of invasive ventilation, vasopressor requirement, duration of vasopressor requirement, and duration of intensive care unit (ICU) stay among the different causes of sepsis and to determine which cause of sepsis had the most severe outcomes. Methods A retrospective chart review was done in critically ill adult patients who were admitted with sepsis to the ICU from July 2017 until July 2019. Acute Physiology and Chronic Health Evaluation (APACHE) IV scores were calculated on patients admitted to ICU on day one of ICU admission. Each patient was then evaluated for outcomes of hospital mortality, need for invasive ventilation, requirement of vasopressors, duration of vasopressors, and duration of ICU stay. The outcomes were then compared between the different sources of sepsis to determine which source of sepsis had the highest severity. Results In total, 176 patients were included in the study. Ninety-three patients were admitted with respiratory sepsis, 26 patients were admitted with gastrointestinal sepsis, 31 patients were admitted with urosepsis, and 26 patients were admitted with other miscellaneous causes of sepsis. The hospital mortality was highest in the respiratory sepsis group at 32%, with a trend towards statistical significance with a P value of 0.057. ICU stay duration was highest in patients with respiratory sepsis at six days, with a statistically significant P value of < 0.001. The need for invasive ventilation was highest in patients with respiratory sepsis at 64%, with a statistically significant P value of < 0.001. The requirement of vasopressor support was highest in patients with respiratory sepsis at 47% and the duration of vasopressors was highest in both respiratory and gastrointestinal sepsis at three days, however, there was no statistical significance. Conclusion Among the different origins of sepsis, the patients with respiratory sepsis had the most severe outcomes, with the highest need for invasive ventilation and the highest ICU stay duration., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Arumairaj et al.)

Objective:  To determine if the QuantiFERON-TB Gold (QFT) testing can be obviated for the diagnosis of latent tuberculosis infection (LTBI) in patients with a positive tuberculin skin test (TST) and a history of Bacillus Calmette-Guerin (BCG) vaccination by identifying high-risk features in patients with positive TST and a history of BCG vaccination who are associated with positive QFT., Methods:  Retrospective chart review was done for 76 adult patients by dividing them into two groups. Group 1 consisted of true positive TST patients who had BCG vaccination and were positive for QFT. Group 2 consisted of false positive TST patients who had BCG vaccination but were negative for QFT. The two groups were compared to determine if the high-risk features of TST induration diameter of 15mm and more, TST induration of 20mm and more, recent immigration to the US, the advanced age of more than 65 years, country of origin with high TB burden, known exposure to active TB, and smoking history were more prevalent in Group 1 compared to Group 2., Results:  Group 1 had 23 patients and Group 2 had 53 patients. Group 1 had a higher prevalence of patients with PPD induration of more than 10mm than Group 2, which was statistically significant with a P value of 0.03. Other risk factors of advanced age, exposure to active TB and smoking did not show statistically significant differences between Groups 1 and 2.  Conclusion: This study also confirms that if the TST induration is more than 10mm in patients with a history of BCG vaccination, the TST induration is likely because of LTBI and is less likely because of cross-reaction with BCG vaccination., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Arumairaj et al.)

Depression is highly prevalent and is associated with poor quality of life and increased mortality among adults with chronic kidney disease (CKD), including those with end-stage renal disease (ESRD). However, there are several important differences in the diagnosis, epidemiology, and management of depression between patients with non-dialysis-dependent CKD and ESRD. Understanding these differences may lead to a better understanding of depression in these 2 distinct populations. First, diagnosing depression using self-reported questionnaires may be less accurate in patients with ESRD compared with CKD. Second, although the prevalence of interview-based depression is approximately 20% in both groups, the risk factors for depression may vary. Third, potential mechanisms of depression might also differ in CKD versus ESRD. Finally, considerations regarding the type and dose of antidepressant medications vary between CKD and ESRD. Future studies should further examine the mechanisms of depression in both groups, and test interventions to prevent and treat depression in these populations.

Objective While albuminuria is a marker for progressive chronic kidney disease (CKD) in patients with type 2 diabetes (T2DM), both albuminuric and normoalbuminuric patients appear prone to vascular injury. This pilot study examines the association between circulating endothelial cell (CEC) levels and vascular injury in patients with T2DM and CKD. Methods In this cross-sectional study, eligible adult patients had T2DM, and stage 3 CKD (estimated glomerular filtration rate between 30 and 60 mL/min/1.73m (2)). CEC levels were tested by Janssen Diagnostics, LLC using an immuno-magnetic bead-based assay. CEC levels were compared to levels in a previously tested normal population. Correlations between CEC levels and other vascular injury markers (urine albumin, von-Willebrand factor antigen, hs-CRP, uric acid) were performed. Results Patients included 40 adults of which nineteen were normoalbuminuric.  Mean CEC levels (38.7, SD 38.1 cells) were significantly higher than the normal population (M = 21±18 cells, p<0.001; N = 249), including in the normoalbuminuric subgroup (M = 42.9±42.5 cells, p<0.001). CEC levels were significantly correlated with uric acid levels (r=0.33, p=0.039). Conclusions CEC levels in patients with T2DM and CKD, both albuminuric and normoalbuminuric, are significantly higher than a normal population, suggesting the presence of vascular injury in both groups. Future studies are needed to evaluate the role of CECs as a biomarker to predict outcomes in normoalbuminuric patients with CKD.

Hyponatremia is the most common electrolyte abnormality. Its diagnostic and therapeutic approaches are in a state of flux. It is evident that hyponatremic patients are symptomatic with a potential for serious consequences at sodium levels that were once considered trivial. The recommendation to treat virtually all hyponatremics exposes the need to resolve the diagnostic and therapeutic dilemma of deciding whether to water restrict a patient with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or administer salt and water to a renal salt waster. In this review, we briefly discuss the pathophysiology of SIADH and renal salt wasting (RSW), and the difficulty in differentiating SIADH from RSW, and review the origin of the perceived rarity of RSW, as well as the value of determining fractional excretion of urate (FEurate) in differentiating both syndromes, the high prevalence of RSW which highlights the inadequacy of the volume approach to hyponatremia, the importance of changing cerebral salt wasting to RSW, and the proposal to eliminate reset osmostat as a subtype of SIADH, and finally propose a new algorithm to replace the outmoded volume approach by highlighting FEurate. This algorithm eliminates the need to assess the volume status with less reliance on determining urine sodium concentration, plasma renin, aldosterone and atrial/brain natriuretic peptide or the BUN to creatinine ratio.

Background: Kidney disease is under-documented in physician notes. The use of template-guided notes may improve physician recognition of kidney disease early in training., Objective: The objective of this study was to determine whether a computerized inpatient renal template note with clinical decision support improves resident knowledge and documentation of kidney disease., Methods: In this prospective study, first year medical residents were encouraged to use the renal template note for documentation over a one-month period. The renal template note included an option for classification of acute kidney injury (AKI) and chronic kidney disease (CKD) categories with a link to standard classifications. Pre- and post-knowledge of AKI and CKD categories was tested with a quiz and surveys of resident experience with the intervention were conducted. Appropriate AKI and/or CKD classification was determined in 100 renal template notes and 112 comparable historical internal medicine resident progress notes from approximately one year prior., Results: 2,435 inpatient encounters amongst 15 residents who participated were documented using the renal template note. A significantly higher percent of residents correctly staged earlier stage CKD (CKD3) using the renal template note compared to historical notes (9/46 vs. 0/33, p<0.01). Documentation of AKI and more advanced CKD stages (CKD4 and 5) did not improve. Knowledge based on quiz scores increased modestly but was not significant. The renal template note was well received by residents and was perceived as helping improve knowledge and documentation of kidney disease., Conclusion: The renal template note significantly improved staging of earlier stage CKD (CKD3) with a modest but non-significant improvement in resident knowledge. Given the importance of early recognition and treatment of CKD, future studies should focus on teaching early recognition using template notes with supplemental educational interventions.

Kidney transplantation is the preferred clinical and most cost-effective option for end-stage renal disease. Significant advances have taken place in the care of the transplant patients with improvements in clinical outcomes. The optimization of the costs of transplantation has been a constant goal as well. We present herein the impact in financial outcomes of a shortened length of stay after kidney transplant.

The most dramatic development in medical decision-making technology has been the advent of the Internet. This has had an impact not only on clinicians, but has also become an important resource for patients who often approach their doctors with medical information they have obtained from the Internet.  Increasingly, medical students, residents and attending physicians have been using the Internet as a tool for diagnosing and treating disease. Internet-based resources that are available take various forms, including informational websites, online journals and textbooks, and social media.  Search engines such as Google have been increasingly used to help in making diagnoses of disease entities. Do these search methods fare better than experienced heuristic methods? In a small study, we examined the comparative role of heuristics versus the 'Google' mode of thinking. Internal medicine residents were asked to "google" key words to come up with a diagnosis. Their results were compared to experienced nephrology faculty and fellows in training using heuristics and no additional help of internet. Overall, with the aid of Google, the novices (internal medicine residents) correctly diagnosed renal diseases less often than the experts (the attendings) but with the same frequency as the intermediates (nephrology fellows).  However, in a subgroup analysis of both common diseases and rare diseases, the novices correctly diagnosed renal diseases less often than the experts but more often than the intermediates in each analysis.  The novices correctly diagnosed renal diseases with the same frequency as nephrology fellows in training.

Catheterization of the urinary bladder during kidney transplantation is essential. The optimal time to remove the Foley catheter postoperatively is not universally defined. It is our practice to remove the Foley catheter on postoperative day 1 in live donor kidney transplant recipients who meet our standardized protocol criteria. We believe that early removal of Foley catheters increases patient comfort and mobility, decreases the risk of catheter associated urinary tract infections, and allows for decreased hospital length of stay. The hypothetical risk of early removal of Foley catheters would be the increased risk of urine leak. We reviewed 120 consecutive live donor kidney transplant recipients and found that there was not an increased incidence of urine leaks in patients whose Foley catheters were removed on postoperative day 1.

Although many anticipate that there will be an eventual shortage of practicing nephrologists, a complete understanding is lacking regarding the current factors that lead US adult nephrology fellows to choose nephrology as a career and their satisfaction with this choice. It is of great concern that interest in obtaining nephrology fellowship training continues to decline in the United States, especially among US medical graduates, and the reasons for this are unclear. The exposure that students and residents have to nephrology is likely to play an important role in the career choices that they make and their ultimate satisfaction with this career choice is likely influenced by several factors, including job opportunities. Some of the findings presented here suggest that there may be a high percentage of nephrology fellows who are dissatisfied with their career choice. Failure to understand the factors that influence trainees to choose nephrology as a career and those that affect their satisfaction with this choice may impair the ability to graduate a sufficient number of nephrologists to meet projected demand. In this article, a number of variables related to the choice of nephrology as a career and satisfaction with a career in nephrology are discussed. Some steps that the nephrology training community might take to help promote interest in nephrology and optimize the satisfaction that nephrology graduates derive from their careers are also proposed.

Evaluation of the potential kidney donor is a complex activity that differs substantially from other types of preoperative assessments. The well being of the donor, who derives no medical benefit from this surgery, must be assured in both the short term and long term, and the potential adverse consequences to the recipient must be determined as well. The criteria that must be met for a person to donate a kidney are rigorous and include medical, social, psychosocial, ethical, and legal issues. Donor evaluation can be divided into assessments to protect the health and safety of the donor and assessments to protect the health and safety of the recipient. This article provides an approach to evaluating a donor, focusing on the complex issues that an evaluator is faced with. A careful assessment of risks and benefits to both the donor and recipient can lead to favorable outcomes.

Patients with end-stage renal disease treated by hemodialysis have enhanced oxidative stress that may result in oxidation of IgG and resultant functional changes. In this study, Western blot analysis was used to assess the oxidized protein content of IgG samples purified from plasma of 8 controls and 11 patients on hemodialysis. In certain experiments, oxidized IgG was digested with papain and Western blot analysis was performed to identify oxidized Fc fragments. Compared to plasma IgG from controls, the IgG from hemodialysis patients had greater oxidized protein content, evidenced by more intense antibody binding to both the heavy and light chains. Western blot analysis of papain digests of oxidized IgG samples that were reprobed with an anti-Fc fragment antibody showed oxidative modification of the Fc fragment. These results suggest that patients with end-stage renal disease treated by hemodialysis have increased oxidized IgG in their plasma, including the Fc portion. Further studies are needed to see if this is due to enhanced production and/or decreased clearance of oxidized IgG.

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease., (Copyright 2003 Wiley-Liss, Inc.)

Background: Oxygen radicals are believed to play a significant role in glomerular disease. In part this may be due to oxidation of lipids, but protein oxidation may play a contributory role as well. We have demonstrated that the mesangial extracellular matrix is susceptible to metal-catalyzed oxidation and that this increases scavenger receptor-mediated adhesion of macrophages, cells which appear to be important participants in glomerular injury via their secretory products. As other scavenger receptor ligands can increase macrophage nitric oxide generation, we examined whether oxidation of matrix could increase the activity of macrophage inducible nitric oxide synthase (iNOS)., Methods: Extracellular matrix was oxidized using a metal-catalyzed oxidation system. Matrix oxidation was measured using carbonyl analysis, and iNOS activity in macrophages seeded onto the matrix was measured by nitrite determination and Western and Northern analyses for iNOS., Results: Macrophages exposed to oxidized matrix demonstrated a significant enhancement of iNOS activity. This enhancement could be antagonized by cotreatment of matrix with the radical spin trap N-tert-butyl-a-phenylnitrone, resulting in a corresponding decrease in protein carbonyl content, a measure of protein oxidation. Seeding macrophages onto oxidized matrix and adding the scavenger receptor ligand polyinosinic acid further augmented iNOS activity, suggesting that additional scavenger receptors were available to bind ligand and that further augmentation of iNOS activity did not require an additional change in cell shape. Western blot analysis revealed an increase in iNOS protein expression as a consequence of interaction with the oxidized matrix, but there was no difference in iNOS mRNA expression by Northern analysis suggesting a post-transcriptional mechanism for enhanced iNOS activity., Conclusion: These data demonstrate that oxidation of extracellular matrix enhances macrophage nitric oxide generation, and suggest a previously undescribed role for extracellular matrix modification in the regulation of cellular function and possibly the mediation of glomerular injury.

Intimal hyperplasia of vascular smooth muscle cells (VSMC) at the venous anastomosis of arteriovenous grafts represents the most common cause of vascular access failure in hemodialysis patients. Upstream release of growth factors from leukocytes activated by adhesion to the graft material may play a role in this lesion. We evaluated the effect of interaction of peripheral blood mononuclear cells (PBMC) with polytetrafluoroethylene (PTFE) on proliferation of VSMC. Vascular smooth muscle cell proliferation was significantly increased by conditioned media from human PBMC incubated with PTFE. Peripheral blood mononuclear cell adhesion to PTFE could not be antagonized by the beta 1 integrin ligand-containing peptide GRGDSP, but was attenuated by EDTA consistent with beta 2 integrin-mediated adhesion. Soluble scavenger receptor ligands at high concentrations had no effect on adhesion to PTFE excluding any contributory role of scavenger receptors in this interaction. Neutralizing antibodies to TNF-alpha significantly attenuated the mitogenic effect of PBMC/PTFE conditioned media and a marked increase in TNF-alpha secretion by PBMC on PTFE was detected by ELISA. These studies demonstrate that PBMC interaction with PTFE can promote proliferation of VSMC via increased production of TNF-alpha and perhaps other cytokines. Leukocyte interaction with PTFE causing enhanced secretion of TNF-alpha and consequent VSMC proliferation may account for the development of venous intimal hyperplasia in hemodialysis patients with arteriovenous grafts.

In attempting to identify variables that might account for the frequent absence of edema in HIV-infected patients with end-stage renal disease, we evaluated 24 consecutive patients at our institution who had HIV infection and developed end-stage renal disease. Clinical and laboratory data prior to the initiation of hemodialysis were recorded and compared between patients with and without edema. Only 11 of the 24 study patients had edema while the remainder did not. The prevalence of diarrhea was significantly less in patients with edema (one of 11 patients compared to eight of 13 with no edema, p < 0.02, odds ratio 0.063). Prior weight loss was significantly less in the patients with edema (9.1 +/- 1.3 kg vs 15.5 +/- 2.2 kg, p < 0.05). Use of antiretroviral therapy was significantly greater in patients with edema (p < 0.05, odds ratio 10.1). None of the patients were receiving diuretics. Blood pressure was significantly higher (p < 0.001) in patients with edema, and serum albumin was low in both groups but did not differ (edema, 24 +/- 2 g/L; no edema, 21 +/- 3 g/L). Four patients had albumin levels as low as 2, 8, 9, and 10 g/L, yet they had no edema. CD4 counts were lower in patients without edema (62 +/- 16 x 10(6) cells/L vs 283 +/- 38 x 10(6) cells/L, p < 0.001). Absence of diarrhea was predictive of the presence of edema with a sensitivity of 91% and specificity of 62% while mean arterial blood pressure > 95 mm Hg was predictive of the presence of edema with a sensitivity of 82% and specificity of 77%. CD4 of > 100 x 10(6) cells/L was predictive of the presence of edema with a sensitivity of 91% and specificity of 77%. These data support the hypothesis that hemodynamic factors may play a role in the frequent absence of edema in patients with HIV infection and renal failure, and variables including diarrhea, low blood pressure, weight loss, and more advanced stage of HIV infection may account for this observation. Hence, the absence of edema should not dissuade the clinician from considering the possibility of advanced renal failure in HIV-infected patients.

Hyperlipidemia has been demonstrated to contribute to hypercellularity of the mesangium in experimental animal models of glomerulosclerosis. We studied whether it also has the potential to convert a hypercellular mesangium into a hypocellular one by inducing mesangial cell (MC) apoptosis. Low density lipoprotein (LDL) enhanced (P < 0.001) mouse mesangial cell (MMC) proliferation at lower concentrations (control, 10.3 +/- 0.3 vs. LDL 100 micrograms/ml, 24.2 +/- 0.3 x 10(4) cells/ml) but augmented (P < 0.001) apoptosis at higher concentrations (control, 5.6 +/- 0.5% vs. LDL, 500 micrograms/ml 26.2 +/- 3.4% apoptotic cells/field). Oxidized (OX) LDL enhanced MMC apoptosis in concentrations of 50 to 200 micrograms/dl. There was a direct relationship between MMC apoptosis and oxidation of LDL as judged by measuring thiobarbituric acid reactive species (TBARS). Since superoxide dismutase (SOD) attenuated (P < 0.001) LDL-induced MMC apoptosis, it seems to be mediated through the generation of free radicals by mesangial cells (control, 4.3 +/- 1.5%; LDL, 200 micrograms/ml, 19.4 +/- 0.5%; LDL + SOD, 8.1 +/- 1.3% apoptotic cells/field). LDL also induced a similar effect on human mesangial cells. These studies were further confirmed by DNA fragment assays and ELISA for programmed cell death. LDL treated cells also showed enhanced mRNA expression for RSG-2, a marker for active cell death. These in vitro results provide a basis for the speculation that LDL has the potential to cause an initial hypercellular and subsequent hypocellular mesangium in the course of the development of glomerulosclerosis.

Glomerular mesangial injury is the predominant renal lesion in patients with heroin addition. We studied the effect of morphine (an active metabolite of heroin)activated macrophages on mesangial cell (MC) proliferation and matrix synthesis. We prepared conditioned media containing either vehicle along (CSP), macrophage secretory products (MSP) and secretory products of morphine treated macrophages (M-MSP), M-MSP increased (P < 0.01) the proliferation of MC when compared with MSP alone. M-MSP increased synthesis of laminin by MC at concentrations of 10 to 50% when compared with cells treated with MSP alone (at 50% concentration, MSP, 126 +/- 19 vs. M-MSP, 312 +/- 14 ng/mg protein, P < 0.001). M-MSP also increased the synthesis of collagen type IV by MC. This effect of M-MSP was attenuated (P < 0.05) by anti-TGF-beta antibodies. Since M-MSP also increased mRNA expression for TGF-beta by MC, it appears that the effected of M-MSP on MC may be mediated through the generation of TGF-beta.

Uptake of immunoglobulin G (IgG) complexes by macrophages (M phi) may play an important role in disease states characterized by increased levels of circulating immune complexes. In sites such as the glomerular mesangium M phi may be subjected to repetitive mechanical strain, although in vitro studies of M phi endocytosis are typically carried out with cells grown on rigid surfaces. We undertook the present study to determine whether repetitive mechanical strain could modulate M phi endocytosis of IgG complexes. IgG complex uptake was significantly diminished in M phi that were subjected to repetitive mechanical strain using parameters corresponding to peak and minimal intraglomerular pressures compared with control, and uptake varied according to the amount of mechanical strain applied. There was no significant difference in surface binding of IgG between M phi subjected to strain and those not. Mechanical strain did not significantly influence the rate of IgG complex degradation. Inhibition of nitric oxide synthase and guanylate cyclase activity did not alter the effect of mechanical strain, although this effect was potentiated by 3-isobutyl-1-methylxanthine (IBMX). Angiotensin II, which has been shown to reduce adenosine 3',5'-cyclic monophosphate (cAMP) production in M phi, significantly attenuated the suppressive effect of mechanical strain on IgG complex uptake as well as another inhibitor of cAMP generation, indomethacin. Enzyme immunoassay demonstrated significantly enhanced levels of cAMP in M phi that were subjected to mechanical strain compared with control, an effect that was potentiated by IBMX and attenuated by angiotensin II and indomethacin. These results demonstrate that repetitive mechanical strain significantly reduces IgG complex uptake by M phi, most likely by enhancing cAMP synthesis. Such an effect might play a significant role in macromolecule handling by M phi in sites in which they are subjected to repetitive mechanical deformation such as the glomerular mesangium.

Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection.