Chronic Kidney Disease in the Older Adult Patient with Diabetes.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and older adult individuals. DM may accelerate the aging process, and the age-related declines in the estimated glomerular filtration rate (eGFR) can pose a challenge to diagnosing diabetic kidney disease (DKD) using standard diagnostic criteria especially with the absence of severe albuminuria among older adults. In the presence of CKD and DM, older adult patients may need multidisciplinary care due to susceptibility to various health issues, e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to older adults. We review the evidence that the benefits from these newer therapies apply equally to older and younger patients with CKD and diabetes type 2 and propose a comprehensive management. This framework will address nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), sodium glucose co-transporter 2 inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and glucagon like peptide 1 receptor agonists (GLP1-RAs).

A closer look at weight loss interventions in primary care: a systematic review and meta-analysis.

Purpose: The major aims were to quantify patient weight loss using various approaches adminstered by a primary care provider for at least 6 months and to unveil relevant contextual factors that could improve patient weight loss on a long-term basis. Methods: A systematic review and meta-analysis was conducted using Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science from inception to December 5, 2022. COVIDENCE systematic review software was used to identify and abstract data, as well as assess data quality and risk of bias. Results: Seven studies included 2,187 people with obesity testing (1) anti-obesity medication (AOM), (2) AOM, intensive lifestyle counseling + meal replacements, and (3) physician training to better counsel patients on intensive lifestyle modification. Substantial heterogeneity in the outcomes was observed, as well as bias toward lack of published studies showing no effect. The random effect model estimated a treatment effect for the aggregate efficacy of primary care interventions -3.54 kg (95% CI: -5.61 kg to -1.47 kg). Interventions that included a medication component (alone or as part of a multipronged intervention) achieved a greater weight reduction by -2.94 kg (p < 0.0001). In all interventions, efficacy declined with time (reduction in weight loss by 0.53 kg per 6 months, 95% CI: 0.04-1.0 kg). Conclusion: Weight loss interventions administered by a primary care provider can lead to modest weight loss. Weight loss is approximately doubled if anti-obesity medication is part of the treatment. Nevertheless, attenuated weight loss over time underscores the need for long-term treatment. Systematic review registration: [https://www.crd.york.ac.uk/prospero/ CRD4202121242344], identifier (CRD42021242344).

Rapid implementation of an emergency on-site CKRT dialysate production system during the COVID-19 pandemic.

BACKGROUND: On December 29, 2021, during the delta wave of the Coronavirus Disease 2019 (COVID-19) pandemic, the stock of premanufactured solutions used for continuous kidney replacement therapy (CKRT) at the University of New Mexico Hospital (UNMH) was nearly exhausted with no resupply anticipated due to supply chain disruptions. Within hours, a backup plan, devised and tested 18 months prior, to locally produce CKRT dialysate was implemented. This report describes the emergency implementation and outcomes of this on-site CKRT dialysate production system. METHODS: This is a single-center retrospective case series and narrative report describing and reporting the outcomes of the implementation of an on-site CKRT dialysate production system. All adults treated with locally produced CKRT dialysate in December 2021 and January 2022 at UNMH were included. CKRT dialysate was produced locally using intermittent hemodialysis machines, hemodialysis concentrate, sterile parenteral nutrition bags, and connectors made of 3-D printed biocompatible rigid material. Outcomes analyzed included dialysate testing for composition and microbiologic contamination, CKRT prescription components, patient mortality, sequential organ failure assessment (SOFA) scores, and catheter-associated bloodstream infections (CLABSIs). RESULTS: Over 13 days, 22 patients were treated with 3,645 L of locally produced dialysate with a mean dose of 20.0 mL/kg/h. Fluid sample testing at 48 h revealed appropriate electrolyte composition and endotoxin levels and bacterial colony counts at or below the lower limit of detection. No CLABSIs occurred within 7 days of exposure to locally produced dialysate. In-hospital mortality was 81.8% and 28-day mortality was 68.2%, though illness severity was high, with a mean SOFA score of 14.5. CONCLUSIONS: Though producing CKRT fluid with IHD machines is not novel, this report represents the first description of the rapid and successful implementation of a backup plan for local CKRT dialysate production at a large academic medical center in the U.S. during the COVID-19 pandemic. Though conclusions are limited by the retrospective design and limited sample size of our analysis, our experience could serve as a guide for other centers navigating similar severe supply constraints in the future.

Rapid remodeling of the soil lipidome in response to a drying-rewetting event.

BACKGROUND: Microbiomes contribute to multiple ecosystem services by transforming organic matter in the soil. Extreme shifts in the environment, such as drying-rewetting cycles during drought, can impact the microbial metabolism of organic matter by altering microbial physiology and function. These physiological responses are mediated in part by lipids that are responsible for regulating interactions between cells and the environment. Despite this critical role in regulating the microbial response to stress, little is known about microbial lipids and metabolites in the soil or how they influence phenotypes that are expressed under drying-rewetting cycles. To address this knowledge gap, we conducted a soil incubation experiment to simulate soil drying during a summer drought of an arid grassland, then measured the response of the soil lipidome and metabolome during the first 3 h after wet-up. RESULTS: Reduced nutrient access during soil drying incurred a replacement of membrane phospholipids, resulting in a diminished abundance of multiple phosphorus-rich membrane lipids. The hot and dry conditions increased the prevalence of sphingolipids and lipids containing long-chain polyunsaturated fatty acids, both of which are associated with heat and osmotic stress-mitigating properties in fungi. This novel finding suggests that lipids commonly present in eukaryotes such as fungi may play a significant role in supporting community resilience displayed by arid land soil microbiomes during drought. As early as 10 min after rewetting dry soil, distinct changes were observed in several lipids that had bacterial signatures including a rapid increase in the abundance of glycerophospholipids with saturated and short fatty acid chains, prototypical of bacterial membrane lipids. Polar metabolites including disaccharides, nucleic acids, organic acids, inositols, and amino acids also increased in abundance upon rewetting. This rapid metabolic reactivation and growth after rewetting coincided with an increase in the relative abundance of firmicutes, suggesting that members of this phylum were positively impacted by rewetting. CONCLUSIONS: Our study revealed specific changes in lipids and metabolites that are indicative of stress adaptation, substrate use, and cellular recovery during soil drying and subsequent rewetting. The drought-induced nutrient limitation was reflected in the lipidome and polar metabolome, both of which rapidly shifted (within hours) upon rewet. Reduced nutrient access in dry soil caused the replacement of glycerophospholipids with phosphorus-free lipids and impeded resource-expensive osmolyte accumulation. Elevated levels of ceramides and lipids with long-chain polyunsaturated fatty acids in dry soil suggest that lipids likely play an important role in the drought tolerance of microbial taxa capable of synthesizing these lipids. An increasing abundance of bacterial glycerophospholipids and triacylglycerols with fatty acids typical of bacteria and polar metabolites suggest a metabolic recovery in representative bacteria once the environmental conditions are conducive for growth. These results underscore the importance of the soil lipidome as a robust indicator of microbial community responses, especially at the short time scales of cell-environment reactions. Video Abstract.

Hypertonic Saline Infusion for Hyponatremia: Limitations of the Adrogué-Madias and Other Formulas.

Hypertonic saline infusion is used to correct hyponatremia with severe symptoms. The selection of the volume of infused hypertonic saline ( VInf ) should address prevention of overcorrection or undercorrection. Several formulas computing this VInf have been proposed. The limitations common to these formulas consist of (1) failure to include potential determinants of change in serum sodium concentration ([ Na ]) including exchanges between osmotically active and inactive sodium compartments, changes in hydrogen binding of body water to hydrophilic compounds, and genetic influences and (2) inaccurate estimates of baseline body water entered in any formula and of gains or losses of water, sodium, and potassium during treatment entered in formulas that account for such gains or losses. In addition, computing VInf from the Adrogué-Madias formula by a calculation assuming a linear relation between VInf and increase in [ Na ] is a source of errors because the relation between these two variables was proven to be curvilinear. However, these errors were shown to be negligible by a comparison of estimates of VInf by the Adrogué-Madias formula and by a formula using the same determinants of the change in [ Na ] and the curvilinear relation between this change and VInf . Regardless of the method used to correct hyponatremia, monitoring [ Na ] and changes in external balances of water, sodium, and potassium during treatment remain imperative.

Ambulatory blood pressure monitoring and peri-hemodialysis blood pressures in a southeast US hemodialysis unit.

AIMS: End-stage renal disease (ESRD) patients on dialysis are perceived to have difficult-to-control blood pressure (BP) and commonly treated with complex antihypertensive regimens. Our hypothesis was that peri-dialysis BP will overestimate the true burden of hypertension in these patients. SUBJECTS AND METHODS: We performed 44-h ambulatory blood pressure monitoring (ABPM) in 43 patients recruited from the University of Mississippi outpatient dialysis unit. Data collected included routine peri-dialysis blood systolic blood pressure (SBP), diastolic blood pressure (DBP), weight gain, and demographic information. We investigated whether the pre-dialysis or post-dialysis blood pressure would better correspond to the ABPM results. RESULTS: The mean age of participants was 50.5 ± 12.05 years, 95% African-American, and 44% diabetic with an average dialysis vintage of 31.1 ± 30 months. The mean SBP and DBP were 164.6/87.9 mmHg ± 22.3/15 before dialysis, 151.5/81.3 mmHg ± 24.1/13 after dialysis and 136/80.6 mmHg ± 23.5/14.7 during ABPM. There were wide limits of agreements between peri-dialysis BP and ABPM, the largest with pre-dialysis SBP (28.5 ± 16.6 mmHg) and the least with post-dialysis DBP (0.7 ± 10 mmHg). With both peri-dialysis BP measurements as explanatory variables in a linear regression model, only the post-dialysis SBP (ß 0.716; p < 0.001) but not pre-dialysis SBP (ß 0.157; p = 0.276) had a significant independent association with ABPM systolic BP. For DBP, both pre-dialysis (ß 0.543; p = 0.001) and post-dialysis (ß 0.317; p = 0.037) values retained correlation with DBP on ABPM. CONCLUSION: Peri-dialysis measurements overestimated true BP burden in this Southeastern U.S. cohort of ESRD patients. When BP readings from outside the dialysis unit are notavailable, assessment of BP control should focus pre-dialysis on DBP and post-dialysison both SBP and DBP.

Volume-related weight gain and subsequent mortality in acute renal failure patients treated with continuous renal replacement therapy.

Fluid overload is a frequent finding in critically ill patients suffering from acute kidney injury (AKI). To assess the impact of fluid overload on the mortality of AKI patients treated with continuous renal replacement therapy (CRRT), we used a registry of 81 critically ill patients with AKI initiated on CRRT assembled over an 18-month period to conduct a cross- sectional analysis using volume-related weight gain (VRWG) of > or =10% and > or =20% of body weight and oliguria (< or =20 ml/h) as the principal variables, with the primary outcome measure being mortality at 30 days. Mean Apache II scores were 27.5 +/- 6.9 with overall cohort mortality of 50.6%. Mean (+/-SD) VRWG was 8.3 +/- 9.6 kg, representing a 10.2% +/- 13.5% increase since admission. Oliguria was present in 65.4% of patients. Odds ratio (OR) for mortality on univariate analysis was increased to 2.62 [95% confidence interval (CI): 1.07-6.44] by a VRWG > or =10% and to 3.22 (95% CI: 1.23-8.45) by oliguria. VRWG > or =20% had OR of 3.98 (95% CI: 1.01-15.75; p = 0.049) for mortality. Both VRWG > or =10% (OR 2.71, p = 0.040) and oliguria (OR 3.04, p = 0.032) maintained their statistically significant association with mortality in multivariate models that included sepsis and Apache II score. In conclusion, fluid overload is an important prognostic factor for survival in critically ill AKI patients treated with CRRT. Further studies are needed to elicit mechanisms and develop appropriate interventions.

Mentoring for subspecialty training program directors: an unrecognized, unmet need?

BACKGROUND: The benefits of mentoring residents have been studied, but there is no research about mentoring new program directors. Program directors' responsibilities have become increasingly complicated, and they may not be adequately prepared for their role at the time of appointment without the benefit of mentoring that is specific to their new role. OBJECTIVE: To assess whether nephrology subspecialty program directors were specifically mentored and whether they felt prepared for the educational and administrative aspects of this role. METHODS: We conducted an electronic needs assessment survey of the nephrology subspecialty program directors through the American Society of Nephrology listserv for program directors. RESULTS: The survey response rate was 42% (58 of 139). Of the respondents, 58% did not feel adequately prepared when they first became subspecialty program directors, and only 32% reported having formal or informal mentoring for the role. Individuals who had served as associate program directors (34%) were more likely to report mentoring than those who had not (P  =  .02). Eighty percent of respondents reported that mentoring from another nephrology program director would have been beneficial during their first several years. CONCLUSIONS: This appears to be the first study specifically evaluating mentoring experiences relevant to the role of nephrology program director. As a result of this survey, the American Society of Nephrology Training Program Director Executive Committee recognized the need to provide opportunities for mentoring new nephrology program directors and formed a New Training Program Director Training and Mentoring Work Group to recommend initiatives for mentoring and training new program directors. Further investigation is needed to assess whether mentoring benefits subspecialty program directors and whether these findings can be generalized to other specialties and subspecialties.

Potential renal sequelae in survivors of hantavirus cardiopulmonary syndrome.

Although other hantaviruses are associated with renal manifestations, hantavirus cardiopulmonary syndrome (HCPS) has not been associated with such sequelae. The HCPS survivors were prospectively evaluated for renal complications. Subjects underwent yearly evaluation, laboratory studies, and 24-hour urine collection. Thirty subjects were evaluated after recovery from HCPS with the first follow-up at a median of 7.4 months after discharge. Subjects were a wide age range (18-51) but had an equal gender composition. Eighteen of 30 (60%) returned for > 1 evaluation. Half (15/30) had a 24-hour urine collection with > 150 mg of total protein and 6 had > 300 mg. Seven had a Cockcroft-Gault creatinine clearance (CrClCG) < 90 mL/min/1.73 m2 and 2 were < 60. Fifty-three percent met the definition of chronic kidney disease. Those treated with extracorporeal membrane oxygenation had less renal sequelae (P = 0.035). Our data suggest that renal sequelae may occur in HCPS. Further study of renal complications of New World hantavirus infections are needed.

C-reactive Protein among Community-Dwelling Hypertensives on Single-agent Antihypertensive Treatment.

BACKGROUND: C-reactive protein is a predictor of adverse cardiovascular outcomes. The effect of antihypertensive therapy on C-reactive protein levels is largely unknown. METHOD: We undertook a cross-sectional study of CRP levels among participants with primary hypertension on single-agent anti-hypertensive therapy in the community-based biracial Genetic Epidemiology Network of Arteriopathy cohort. Linear regression models were used to assess the association of anti-hypertensive medication class with log-transformed C-reactive protein after adjustment for age, gender, ethnicity, body mass index, smoking, diabetes, HMG-Co-A reductase inhibitor use, achieved blood pressure control (<140/90 mmHg), serum creatinine and urine albumin-to-creatinine ratios. RESULTS: There were 662 participants in the cohort taking single-agent therapy for hypertension. Median C-reactive protein levels differed across participants: 0.40 mg/dL for those on diuretics, 0.34 mg/dL on calcium channel blockers, 0.25 mg/dL on beta blockers and 0.27 mg/dL on renin-angiotensin-aldosterone system inhibitors (p<0.001). With multivariable adjustment, the group on renin-angiotensin-aldosterone system inhibitors had a 20% lower mean CRP on average than the group on diuretics (p=0.044), differences between other medication classes were not apparent. Heart rate had a strong association with C-reactive protein (p < 0.001). CONCLUSIONS: Antihypertensive medication class may influence inflammation, particularly in patients on RAAS inhibitors.

Pathogenesis and treatment of encapsulating peritoneal sclerosis: basic and translational research.

Encapsulating peritoneal sclerosis is a devastating condition in long-term peritoneal dialysis patients. Animal models have employed chemical insults to simulate its pathology and have provided insights into its pathophysiology, which appears to include inflammation, angiogenesis, and fibrosis. Monitoring of biomarkers and interruption of molecular pathways have provided potential interventions to slow or prevent the disease process. However, there remain many questions concerning the trigger that alters chronic peritoneal inflammation in peritoneal dialysis to severe sclerosis, peritoneal adhesions, and bowel obstruction. Further advances in therapy will likely require an effective means of an early diagnosis through related biomarkers, which in turn will require further advances in the understanding of the pathogenesis of this disease process.

Predictors of mortality in a cohort of intensive care unit patients with acute renal failure receiving continuous renal replacement therapy.

BACKGROUND: Despite the frequent use of continuous renal replacement therapy (CRRT) in the management of acute renal failure (ARF) in the critically ill, predictors of mortality remain unclear. METHODS: A registry of all patients initiated on CRRT at a single institution was assembled over an 18-month period, and a subsequent cross-sectional analysis of selected variables was conducted for associations with mortality. Predictors evaluated were age, gender, diagnosis of sepsis, Apache II score, days between ARF diagnosis and initiation of CRRT, creatinine at initiation of CRRT, change in creatinine from baseline and admission to initiation of CRRT, setting of ARF, and prescribed CRRT dose. The principal outcome was mortality at 30 days. RESULTS: Eighty-one individuals met inclusion criteria. Overall mortality for the study was 50.2%. The mean elevation in creatinine from admission to initiation of CRRT was 1.6 mg/dL (141.4 micromol/L) in those who lived and 2.6 mg/dL (229.8 micromol/L) in those who died (P = 0.023). Patients admitted with normal renal function who developed ARF while in the hospital had mortality of 56.3%. When available, patients with abnormal renal function at presentation were further classified by either abnormal or normal preadmission creatinine. These patients had mortality of 31.3% and 83.3%, respectively. These differences in mortality were statistically significant. CONCLUSIONS: Increased mortality was significantly associated with the magnitude of change in serum creatinine between admission and initiation of CRRT. Also, patient ARF classification was significantly associated with mortality.

Obesity-survival paradox-still a controversy?

Since the original description of the obesity-survival paradox in 1999, which suggested a survival advantage for overweight and obese patients undergoing hemodialysis, a large body of evidence supporting the paradox has accumulated. The reason for the paradox has yet to be defined. Better nutrition may be a partial explanation, or it may be that in uremic milieu, excessive fat and surplus calories might confer some survival advantage. The "surplus calorie theory" as a potential mechanism for the paradox is of great interest. If proven to be correct, it might explain why peritoneal dialysis patients who receive excessive calories through dialysis do not exhibit the paradox and, secondly and more importantly, therapy could be directed to enhance a greater caloric intake by renal failure patients to engender a better survival outcome. Finally, other clinical settings, for example, congestive heart failure, have their own obesity-survival paradox. Thus, the paradox appears to be a wider phenomenon and might merely be the external expression of a larger principle yet to be uncovered.

The obesity-survival paradox in hemodialysis patients: why do overweight hemodialysis patients live longer?

Obesity is increasingly common in the United States, and it frequently coexists with diabetes and hypertension. Given that diabetes and hypertension are the 2 most common causes of end-stage renal disease, it is not surprising that obesity is also highly prevalent in the US hemodialysis population. However, unlike in the general population, obesity is associated with improved survival in hemodialysis patients. This phenomenon, the obesity-survival paradox, is neither universally accepted nor completely understood. In this article, we review the available data and provide potential reasons for the obesity-survival paradox in the dialysis population.

Changing relationship of blood pressure with mortality over time among hemodialysis patients.

High BP is a major risk factor for atherosclerotic cardiovascular disease mortality in the general population. Surprising, studies that have been conducted among hemodialysis (HD) patients have yielded conflicting data on the relationship between BP and mortality. This study explores two hypotheses among HD patients: (1) The relationship between BP and mortality changes over time, and (2) mild to moderate hypertension is well tolerated. Incident HD patients who were treated at Dialysis Clinic Inc. facilities between 1993 and 2003 were studied. Primary end points were atherosclerotic cardiovascular disease and all-cause mortality. The relationship between BP and mortality was analyzed in two sets of Cox proportional hazards models. Model-B explored the relationship between baseline BP and mortality in sequential time periods. Model-TV assessed the relationship between BP, treated as time-varying, and mortality. The study sample (n = 16,959) was similar in characteristics to the United States Renal Data Systems population, although black patients were slightly overrepresented. Model-B demonstrated that the relationship between baseline BP and mortality changes over time. Low systolic BP (<120 mmHg) was associated with increased mortality in years 1 and 2. High systolic BP (> or =150 mmHg) was associated with increased mortality among patients who survived > or =3 yr. Low pulse pressure was associated with increased mortality. Model-TV demonstrated that mild to moderate systolic hypertension may be relatively well tolerated. In conclusion, the relationship between baseline BP and mortality changes over time. Mild to moderate systolic hypertension was associated with only modest increases in mortality.

Sparing of written production of proper nouns and dates in aphasia.

Aphasia is a total or partial loss of the ability to produce or understand language, usually caused by brain disease or injury. In this case study, the aphasic patient (BMW) has a profound impairment of oral production and a very moderate impairment in comprehension. Several years of informal observation lead to the current study that contrasts written naming of common nouns to written naming of proper nouns and dates. BMW named professional ice hockey players, team logos, and provided birthdays of players with near perfect accuracy and normal rates of production. In contrast, his performance on naming common nouns was only 50% accurate and appeared very laborious. The results of this study thus show a clear preservation of date and proper noun production in contrast to common nouns.

Classification of the degree of obesity by body mass index or by deviation from ideal weight.

BACKGROUND: The purpose of this study was to compare classifications of subjects as underweight, normal weight, or obese by body mass index (BMI) and the ratio of body weight to ideal weight (W/IW). METHODS: We performed a theoretical comparison of the 2 indices. We compared classifications of the degree of obesity in 1839 women and 5914 men who were followed up in the primary care clinics of a United States federal hospital. Information was extracted from computerized records. Subjects were classified as underweight (BMI < 18.5 kg/m2, W/IW < 0.9), obese (BMI > or = 30.0 kg/m2, W/IW > or = 1.2), or normal weight (BMI, W/IW values between the cutoff values for underweight and obesity). W/IW values were computed assuming small, medium, and large skeletal frame for all. We compared the classifications of subjects as underweight, normal weight, or obese by BMI and W/IW. We used Cohen's kappa ratio to evaluate the agreement between these classifications. RESULTS: Theoretically, the cutoff values of BMI and W/IW for underweight and obesity are not in agreement. Patient data revealed substantial differences in the classifications of subjects as underweight, normal weight, or obese. Kappa ratios ranged between 0.18 (poor agreement) and 0.71 (reasonable, but not high degree of agreement). In general, kappa ratios were higher when assuming large or medium skeletal frame versus small frame. CONCLUSIONS: There are substantial discrepancies in classifying the subjects of a population as underweight, normal weight, or obese by BMI or W/IW. These discrepancies may cause confusion when 2 or more indices are used simultaneously to classify the degree of obesity.