What Do We Know about Opioids and the Kidney?

Evidence suggests a link between opioid use and kidney disease. This review summarizes the known renal manifestations of opioid use including its role in acute and chronic kidney injury. Both the direct and indirect effects of the drug, and the context which leads to the development of renal failure, are explored. While commonly used safely for pain control and anesthesia in those with kidney disease, the concerns with respect to side effects and toxicity of opioids are addressed. This is especially relevant with the worldwide increase in the use of opioids for medical and recreational use.

Renal function status.

OBJECTIVE: The objective of this article is to review and evaluate the various parameters used in determining renal status. CONCLUSION: The physiologic determination of renal status is the measured glomerular filtration rate (mGFR). Serum creatinine, blood urea nitrogen, cystatin C, and estimated GFR (eGFR), based on serum creatinine have failed to replace mGFR. All physicians should be aware of limitations of substituted mGFR.

Peritoneal dialysis should not be the first choice for renal replacement therapy in the elderly.

Based on our review, it appears fair to infer that substantive differences in long-term outcome with PD compared with in-center HD have not been documented. PD may offer a slight advantage in younger, nondiabetic patients in the early phase of renal replacement therapy. Nevertheless, PD is not an advantageous option for that large cohort of the dialysis population in the United States comprised of elderly patients with diabetes.

Coronary Artery Disease, Cardiac Arrest, and Shared Decision Making in a Recreational Athlete.

A highly active 59-year-old-man with a history of cardiac arrest and myocardial infarction presented for exercise recommendations. Multimodality risk stratification led to ventricular fibrillation cardiac arrest at the completion of a maximal effort cardiopulmonary exercise test. Using shared decision making, the safety and feasibility of returning to exercise were discussed. (Level of Difficulty: Intermediate.).

Noninvasive Vocal Biomarker is Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

OBJECTIVE: To investigate the association of voice analysis with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. PATIENTS AND METHODS: A vocal biomarker, a unitless scalar with a value between 0 and 1, was developed based on 434 voice samples. The biomarker training was followed by a prospective, multicenter, observational study. All subjects were tested for SARS-CoV-2, had their voice recorded to a smartphone application, and gave their informed consent to participate in the study. The association of SARS-CoV-2 infection with the vocal biomarker was evaluated. RESULTS: The final study population included 80 subjects with a median age of 29 [range, 23 to 36] years, of whom 68% were men. Forty patients were positive for SARS-CoV-2. Infected patients were 12 times more likely to report at least one symptom (odds ratio, 11.8; P<.001). The vocal biomarker was significantly higher among infected patients (OR, 0.11; 95% CI, 0.06 to 0.17 vs OR, 0.19; 95% CI, 0.12 to 0.3; P=.001). The area under the receiver operating characteristic curve evaluating the association of the vocal biomarker with SARS-CoV-2 status was 72%. With a biomarker threshold of 0.115, the results translated to a sensitivity and specificity of 85% (95% CI, 70% to 94%) and 53% (95% CI, 36% to 69%), respectively. When added to a self-reported symptom classifier, the area under the curve significantly improved from 0.775 to 0.85. CONCLUSION: Voice analysis is associated with SARS-CoV-2 status and holds the potential to improve the accuracy of self-reported symptom-based screening tools. This pilot study suggests a possible role for vocal biomarkers in screening for SARS-CoV-2-infected subjects.

New-onset diabetes after hemodialysis initiation: impact on survival.

BACKGROUND: The incidence of new-onset diabetes after initiation of hemodialysis (NODAD) and its impact on survival is not known. METHODS: We used data from the United States Renal Data System (USRDS) from January 2000 to December 2001, with at least 3 years of follow-up for this study. Patients aged 18-80 years were included. NODAD was defined as two Medicare institutional claims for diabetes in patients with no history of diabetes prior to starting hemodialysis (HD). Incidence (per 1,000 patient-years), prevalence (%) and hazard ratios for mortality in patients with NODAD were calculated. RESULTS: There were 59,340 incident patients with no history of diabetes prior to starting HD, of which 3,853 met criteria for NODAD. The overall incidence and prevalence of NODAD were 20 per 1,000 patient-years and 7.6%, respectively. In a cohort of 444 patients without diabetes and documented glycosylated hemoglobin A1c, <6% prior to starting HD (from January 2005 and March 2006), at a mean follow-up of 4.7 +/- 2.6 months, 6.8% developed NODAD defined by two Medicare claims for diabetes after initiation of HD. NODAD was associated with a significantly increased risk of death as compared to non-diabetes patients (hazard ratio 1.20, 95% confidence interval 1.14-1.25). CONCLUSION: The USRDS showed a high incidence of NODAD, associated with significantly higher mortality compared to those who did not develop NODAD. The mechanism of NODAD needs to be explored further in experimental and clinical studies.

Stressful ethical issues in uremia therapy.

The objectives of this review are to introduce and explore the following representative ethical problems generated by modern renal replacement therapy: (1) reviewing the historical origin of medical ethics with specific reference to nephrology; (2) recognizing the complex stresses surrounding assignment of a deceased donor renal transplant to a geriatric patient while young patients continue waiting for a donor kidney; and (3) appreciating the concept of futility and support for a uremic patient opting for death rather than further uremia therapy as the best in choice in coping with renal failure.

Continuously evolving management concepts for diabetic CKD and ESRD.

During the past 50 years, a global pandemic of kidney failure attributed to diabetes mellitus provoked continuously changing treatment strategies based in the belief that micro- and macrovascular complications of diabetes may be preventable. Both patient and physician have revised, and sometimes reversed drug regimens based on inferences extracted from prospective, controlled, properly populated trials. Illustrating this dilemma is a newly relaxed target for glycosylated hemoglobin (HbA1c) of 7%, introduced because of the greater rate of cardiovascular complications noted when striving to reduce attained HbA1c to < or = 6.5%. Our concept of the natural history of kidney disease in diabetes has repeatedly been modified by a rising mean age of those developing uremia (now 64.5 years). Underscoring the reality that the majority of diabetic kidney failure patients fall within the geriatric age group. An encouraging finding first reported in 2005 and continuing through 2009 is a declining incidence rate of irreversible advanced kidney failure in individuals known to have diabetes. That this "good news" results from appropriate renoprotective treatment is as yet unsubstantiated wishful thinking.

Long-term outcomes of dual kidney transplantation-a single center experience.

The shortage of kidney donors has led to broadening of the acceptance criteria for deceased donor organs beyond the traditional use of young donors. We determined long-term post-transplant outcomes in recipients of dual expanded criteria donor kidneys (dECD, n = 44) and compared them to recipients of standard criteria donor kidneys (SCD, n = 194) and single expanded criteria donor kidneys (sECD, n = 62). We retrospectively reviewed these 300 deceased donor kidney transplants without primary non-function (PNF) or death in the first two wk, at our center from 1996 to 2003. The three groups were similar in baseline characteristics. Kidney allograft survival and patient survival (nine yr) were similar in the three respective donor groups, SCD, sECD and dECD (60% vs. 59% vs. 64% and 82% vs. 73% vs. 73%). Acute rejection in the first three months was 23.2%, 16.1%, and 22.7% in SCD, sECD and dECD, respectively (p = 0.49) and delayed graft function was 25.2%, 31.9% and 17.1% in the three groups, respectively (p = 0.28). When PNF and death within the first two wk was included, there was no significant difference in graft survival between the three groups. In our population, recipients of dECD transplants have acceptable patient and graft survival with kidneys that would have usually been discarded.

Reassessing marketing of kidneys from the 2008 perspective.

Progressive improvements in all aspects of the kidney transplant regimen establish this form of renal replacement therapy as superior to peritoneal or hemodialysis in terms of extent of rehabilitation and long-term recipient survival. Continuous growth in the number of patients with kidney failure sustained by dialytic therapy has not been associated with substantially increased deceased donor kidney contributions, causing intensified stressful waiting periods for potential recipients lacking a live kidney donor. Neither public relation campaigns nor local government efforts have substantially increased kidney donation. Buying a donor kidney is illegal and condemned as fostering exploitation of poor people by the wealthy. Widely publicized examples of coercion of unwilling donors create a negative image of harmful, inhumane conduct deployed to obtain kidneys sold and transplanted under unsavory circumstances. Yet efforts to establish and test governmental programs to supervise and sustain acceptable standards for the sale and implantation of kidneys from fully informed, medically evaluated and protected, fairly compensated donors have been resisted and frustrated by those who consider such compensation loathsome. Accordingly, while selling kidneys is prohibited by law, pressure from those wanting to quench the number of deaths of wait-listed dialysis patients continues forcing reexamination of an issue that, like prohibition of the possession and sale of alcohol in the United States in 1920, places the will of a people in opposition to unreasonably restrictive laws. The debate continues.

Asymmetric breast enlargement minus central venous thrombosis in a hemodialysis patient.

A 76-year-old woman hemodialysis patient was hospitalized for community-acquired pneumonia complicating chronic obstructive pulmonary disease. End-stage renal disease secondary to hypertension had been diagnosed at the age of 64 for which the patient was initiated on maintenance hemodialysis. Then, she received a deceased donor kidney transplant at the age of 68 that succumbed to chronic rejection 4 years later when she was restarted on hemodialysis. Hemodialysis was performed via a right subclavian vein double lumen catheter for 2 months when a right brachio-axillary graft was inserted. Severe venous congestion, swelling, and nipple tenderness of her right breast noted on admission had been increasing for 6 weeks before hospital admission. No arm swelling was evident. Initial management of the patient's pneumonia and chronic obstructive pulmonary disease consisted of intravenous ceftriaxone and albuterol inhaler to which intravenous oxacillin (1 g q 6 hr) was added for presumed right mastitis. Radiological work-up for masses and malignancies was negative. An angiogram of the right upper extremity detected stenosis of the dialysis access graft at its anastomosis with the axillary vein. Angioplasty of the stenosis was performed without incident or evidence of central vein stenosis. Rapid resolution over 10 days of the unilateral breast congestion followed without complication.

Inpatient diabetes management: examining morning practice in an acute care setting.

PURPOSE: Morning diabetes management in an inpatient acute care facility was examined. METHODS: A descriptive, nonexperimental research design was used to study the effect of the following variables on patients' prelunch blood glucose: duration of time between (1) blood glucose monitoring and insulin administration, (2) insulin administration and breakfast, and (3) blood glucose monitoring and breakfast. A nonprobability convenience sample was used to examine 40 adults with diabetes who were hospitalized in an urban, academic medical center. RESULTS: The chi2 test and measurements of central tendency were used for statistical analysis. The mean interval of time between (1) blood glucose monitoring and insulin administration was 93 minutes+/-52.82, (2) blood glucose monitoring and breakfast was 121+/-47 minutes, and (3) insulin administration and breakfast was 73+/-37.06 minutes. Insulin was administered in 28% of patients<45 minutes before breakfast, whereas in 39% and 33%, it was administered between 46 and 90 minutes and >90 minutes prior to breakfast, respectively. There was a statistically significant difference (P=.033) between mean prelunch glucose levels for subjects who received insulin>45 minutes before breakfast and mean glucose levels for those who received insulin<45 minutes before breakfast. Eighty percent of patients whose breakfast was >45 minutes following insulin had prelunch glucose values of >180 mg/dL (10 mmol/L) versus 20%<180 mg/dL (10 mmol/L). Of those whose breakfast was <45 minutes before insulin, 43% had blood glucose levels>180 mg/dL, and 57% had blood glucose<180 mg/dL (P=.026). A logistical regression model revealed that patients had a 5.3 times higher risk of having a prelunch blood glucose level>180 mg/dL when their breakfast time was >45 minutes after receiving insulin as compared to those whose insulin was given<45 minutes before breakfast (relative risk, 5.3; 95% confidence interval, 1.2-25; P=.031). CONCLUSION: Current practice suggests patients are at a higher risk of prelunch hyperglycemia, and multiple opportunities exist to improve care for the inpatient with diabetes.

Metabolic profiling of a chronic kidney disease cohort reveals metabolic phenotype more likely to benefit from a probiotic.

SCOPE: Persistent reduction in Glomerular Filtration Rate (GFR) is a hallmark of Chronic Kidney Disease (CKD) and is associated with an elevation of Blood Urea Nitrogen (BUN). This metabolomics pilot study sought to identify metabolites that differentiated patients with CKD whose BUN decreased on a probiotic and possible mechanisms. METHODS AND RESULTS: Metabolomics was used to analyze baseline plasma samples previously diagnosed with CKD Stage III-IV. Patients had participated in a dose escalation study of the probiotic Renadyl™. A total of 24 samples were categorized depending on whether BUN increased or decreased from baseline after 4 months of probiotic use. Multivariate analysis was used to analyze the data and determine the metabolites that best differentiated the phenotypic groups. The sixteen patients who had a decrease in BUN were not significantly different based on demographic and clinical measures from those whose BUN increased or did not change with the exception of age. Eleven of the fourteen metabolites that differentiated the groups were known to be modulated by gut microflora, which may eventually provide a mechanistic link between probiotic and outcomes. CONCLUSIONS: Metabolomics revealed metabolites at baseline that may predict individuals with CKD that would most benefit from a probiotics.

In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease.

Chronic kidney disease may progress to end-stage renal disease, which requires dialysis or kidney transplantation. No generally applicable therapies to slow progression of renal disease are available. Bacteriotherapy affords a promising approach to mitigate uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne alkalophilic urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such "enteric dialysis" formulation. Data presented herein suggest that Sp survives through exposure to gastric juice retaining the ability to hydrolyze urea. In vitro, 10 cfu (colony forming units) of Sp removed from 21 +/- 4.7 mg to 228 +/- 6.7 mg urea per hour, depending on pH, urea concentration, and nutrient availability. Beneficial effects of Sp on fermentation parameters in the intestine were demonstrated in vitro in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) inoculated with fecal microbiota. Enumeration of marker organisms suggested that presence of Sp does not disturb microbial community of the SHIME. Additionally, a pilot study in 5/6th nephrectomized rats fed 10 cfu of live Sp daily throughout the study demonstrated that the tested regimen reduced blood urea-nitrogen levels and significantly prolonged the lifespan of uremic animals.

Fourth-Year Medical Student Charting of Older Persons' Cognitive and Functional Status.

BACKGROUND AND OBJECTIVES: Functional and cognitive impairment correlates with medical outcomes in older persons, yet documentation in the medical record is often inadequate. The purpose of this pilot study was to evaluate fourth year (M4) medical students' charting performance of cognition and functional status in older persons during non-geriatric clerkships using an audit tool. METHODS: The research assistants used a chart abstracting tool to retrospectively review patients' charts. The abstracting tool contained keywords and phrases to prompt the research assistants to look for any documentation of patient status in four domains: (1) delirium or acute confusional state, (2) chronic cognitive impairment, (3) activities of daily living, and (4) instrumental activities of daily living. The threshold was any mention of keywords in these domains. RESULTS: On non-geriatrics M4 clerkships in the hospital, students documented acute cognitive status (ACS) and presence or absence of chronic cognitive impairment (CCI) in 57% and 68% of cases respectively, with physicians and/or nurses doing it more often at 63% and 84%. Both students and other care providers documented ACS and CCI in the same charts 41% and 59% of the time, respectively. Students documented activities of daily living (ADLs) and instrumental activities of daily living (IADLs) 31% and 3% respectively, physicians and/or nurses 59% and 0%. CONCLUSIONS: Documentation of cognitive status in hospital charts for students and physicians was somewhat higher than in the literature. This may be because geriatrics is integrated into our 4-year curriculum. Documentation by both students and physicians was better for ADLs than IADLs and poor for IADLs overall.

Patients' understanding of their treatment plans and diagnosis at discharge.

OBJECTIVE: To ascertain whether patients at discharge from a municipal teaching hospital knew their discharge diagnoses, treatment plan (names and purpose of their medications), and common side effects of prescribed medications. PATIENTS AND METHODS: From July to October 1999, we surveyed 47 consecutive patients at discharge from the medical service of a municipal teaching hospital in New York City (Brooklyn, NY). Patients were asked to state either the trade or the generic name(s) of their medication(s), their purpose, and the major side effect(s), as well as their discharge diagnoses. Patients were excluded if they were not oriented to person, place, and time, were unaware of the circumstances surrounding their admission to the hospital, and/or did not speak or understand English. RESULTS: Of the 47 patients surveyed, 4 were excluded. Of the remaining 43 patients, 12 (27.9%) were able to list all their medications, 16 (37.2%) were able to recount the purpose of all their medications, 6 (14.0%) were able to state the common side effect(s) of all their medications, and 18 (41.9%) were able to state their diagnosis or diagnoses. The mean number of medications prescribed at discharge was 3.89. CONCLUSIONS: Less than half of our study patients were able to list their diagnoses, the name(s) of their medication(s), their purpose, or the major side effect(s). Lacking awareness of these factors affects a patient's ability to comply fully with discharge treatment plans. Whether lack of communication between physician and patient is actually the cause of patient unawareness of discharge Instructions or if this even affects patient outcome requires further study.

An introduction to phosphate binders for the treatment of hyperphosphatemia in patients with chronic kidney disease.

Chronic kidney disease has the potential to induce sequelae that can have severe and mortal outcomes. In particular, impaired glomerular filtration can cause a hyperphosphatemic state, which, if left unchecked, can lead to secondary hyperparathyroidism, vascular calcification, and renal osteodystrophy. Therapeutic management of hyperphosphatemia must maintain both phosphorus and calcium serum concentrations within the recommended guidelines. The balance of both minerals is regulated by parathyroid hormone; thus, an imbalance of one affects the other. In end-stage renal disease, patients often present with hypocalcemic levels due to the kidneys' inability to generate active vitamin D to promote calcium absorption in the intestine. Absorption of calcium can be increased by the administration of active vitamin D analogues. Minimizing phosphorus intake through a strict dietary regimen, combined with the use of phosphate binders to absorb excess ingested phosphate, can help to maintain serum phosphate levels near the recommended concentration of 5.5 mg/dL. Phosphate-binding compounds have evolved from the original aluminum-based binders pioneered in the 1970s to calcium-based binders such as calcium acetate, and more recently, to the following additions to the nephrologist's armamentarium: sevelamer--a polyhydrochloride polymer, and lanthanum carbonate. One of the top 2 common clinical treatments for hyperphosphatemia, calcium acetate, has an established history of efficacy since the 1980s, and has been shown to be cost effective and well tolerated, as well.