Intestinal dialysis for conservative management of Uremia.

PURPOSE OF REVIEW: Renal replacement therapies, such as hemodialysis are invasive and impose significant financial burden as well as burden on quality of life. Conservative and 'gentler' forms of renal replacement therapy for the frail and palliative care patient is an unmet medical need. RECENT FINDINGS: The treatment of uremia using the gut as a substitute for the kidney has been proposed but is not practiced widely because of proven lack of long-term mortality benefit coupled with complications like edema and hyperchloremia. Mounting evidence showed that endotoxins from gastrointestinal tract are a major source of chronic inflammation in chronic kidney disease (CKD). The high load of nitrogenous waste elimination through the bowel could potentially serve as an alternative modality to remove uremic wastes especially in people who opt for conservative management for end-stage renal disease with some recent studies in Iran and China showing promising benefits in uremia. SUMMARY: In this review, we will discuss the history, recent evidence and potential of these therapies and their implications in CKD for conservative and easy management of uremia.

Utilization of peritoneal dialysis in the United States: Reasons for underutilization, specifically in New York State and the boroughs of New York City.

Peritoneal dialysis (PD) is currently underutilized in the United States (US), even within resource-rich neighborhoods. We analyzed data from US Renal Data Service to determine PD utilization within the US, New York State (NYS), selected boroughs within New York City (NYC), and Boston, Massachusetts. We then compared the odds of selecting PD with hemodialysis (HD) and analyzed how diabetes mellitus status, age >65 years, gender, and race influenced PD utilization between 2010 and 2016. We then compared a high-volume PD center (HVC) with a low-volume PD center (LVC). The odds of starting PD vs HD were as follows: Brooklyn 0.30 (0.25-0.36; <0.0001), Bronx 0.56 (0.47-0.67; <0.0001), Queens 0.66 (0.54-0.80; <0.0001), and Manhattan 0.61 (0.52-0.71; <0.0001). In 2016, the odds of starting PD compared with the rest of the US were as follows: Brooklyn 0.14 (0.08-0.22; <0.0001), Bronx 0.39 (0.27-0.56; <0.0001), Queens 0.32 (0.23-0.45; <0.0001), Manhattan 0.54 (0.36-0.79; 0.002), and Boston 0.89 (0.58-1.4; 0.624). Analysis of influencing factors showed that only age >65 significantly (<0.0001) influenced PD modality selection in Brooklyn and Boston. Differences between HVC and LVC in terms of modality transition, peritonitis rate, or provider:patient ratio were not statistically significant. Factors that influence PD utilization in urban neighborhoods are discussed and remediation measures are proposed.

Personalized Intervention in Monogenic Stone Formers.

PURPOSE: Treatment of a first-time renal stone consists of acute management followed by medical efforts to prevent stone recurrence. Although nephrolithiasis is roughly 50% heritable, the presence of a family history usually does not affect treatment since most stone disease is regarded as polygenic, ie not attributable to a single gene. Recent evidence has suggested that single mutations could be responsible for a larger proportion of renal stones than previously thought. This intriguing possibility holds the potential to change the management paradigm in stone prevention from metabolically directed therapy to more specific approaches informed by genetic screening and testing. This review synthesizes new findings concerning monogenic kidney stone disease, and provides a concise and clinically useful reference for monogenic causes. It is expected that increased awareness of these etiologies will lead to increased use of genetic testing in recurrent stone formers and further research into the prevalence of monogenic stone disease. MATERIALS AND METHODS: We assembled a complete list of genes known to cause or influence nephrolithiasis based on recent reviews and commentaries. We then comprehensively searched PubMed® and Google Scholar™ for all research on each gene having a pertinent role in nephrolithiasis. We determined which genes could be considered monogenic causes of nephrolithiasis. One gene, ALPL, was excluded since nephrolithiasis is a relatively minor aspect of the disorder associated with the gene (hypophosphatasia). We summarized selected studies and assembled clinically relevant details. RESULTS: A total of 27 genes were reviewed in terms of recent findings, mode of inheritance of stone disease, known or supposed prevalence of mutations in the general population of stone patients and specific therapies or considerations. CONCLUSIONS: There is a distinct opportunity for increased use of genetic testing to improve the lives of pediatric and adult stone patients. Several genes first reported in association with rare disease may be loci for novel mutations, heterozygous disease and forme frustes as causes of stones in the broader population. Cases of idiopathic nephrolithiasis should be considered as potentially having a monogenic basis.

Cryoglobulinemia in a patient with chronic lymphocytic leukemia - A case report and review of literature of renal involvement in CLL.

The incidence of glomerulonephritis, as a manifestation of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), has always been considered low. Though renal infiltration is usually detected at post-mortem, it does not often interfere with kidney function [1]. Though immunoglobulin (Ig) levels in most CLL patients are subnormal, small monoclonal Ig peaks are occasionally detected in serum. They were present in a number of reported CLL nephropathy patients, and not all were cryoglobulins; serum and glomerular staining were concordant for Ig type [2,3,4]. Myeloma, which secretes monoclonal light chains, causes nephropathy in 25% of patients. But the little presumably secreted by small plasma cell clones, without myeloma, may also be nephrotoxic. The same is true of the low secretory CLL cells, which may occasionally be associated with cryoglobulins and other nephrotoxic Igs [5]. We report a patient with early stage CLL (Rai stage 0) with cryoglobulins, which led to membranoproliferative glomerulonephritis (MPGN), and death. We located reports of 51 patients with CLL-associated nephrotic syndrome or nephropathy, mostly from MPGN related to local Ig deposits. In those patients screened for cryoglobulins, about half tested positive. Many were early stage cases, where MPGN developed long after CLL presentation, and responded to its treatment. As early diagnosis and treatment CLL-related nephropathy may be curative, we propose a prospective study to determine the incidence of hyperalbuminuria development after presentation.

Psychosocial intervention improves depression, quality of life, and fluid adherence in hemodialysis.

Patients with ESRD have high rates of depression, which is associated with diminished quality of life and survival. We determined whether individual cognitive behavioral therapy (CBT) reduces depression in hemodialysis patients with elevated depressive affect in a randomized crossover trial. Of 65 participants enrolled from two dialysis centers in New York, 59 completed the study and were assigned to the treatment-first group (n=33) or the wait-list control group (n=26). In the intervention phase, CBT was administered chairside during dialysis treatments for 3 months; participants were assessed 3 and 6 months after randomization. Compared with the wait-list group, the treatment-first group achieved significantly larger reductions in Beck Depression Inventory II (self-reported, P=0.03) and Hamilton Depression Rating Scale (clinician-reported, P<0.001) scores after intervention. Mean scores for the treatment-first group did not change significantly at the 3-month follow-up. Among participants with depression diagnosed at baseline, 89% in the treatment-first group were not depressed at the end of treatment compared with 38% in the wait-list group (Fisher's exact test, P=0.01). Furthermore, the treatment-first group experienced greater improvements in quality of life, assessed with the Kidney Disease Quality of Life Short Form (P=0.04), and interdialytic weight gain (P=0.002) than the wait-list group, although no effect on compliance was evident at follow-up. In summary, CBT led to significant improvements in depression, quality of life, and prescription compliance in this trial, and studies should be undertaken to assess the long-term effects of CBT on morbidity and mortality in patients with ESRD.

Reimbursement of dialysis: a comparison of seven countries.

Reimbursement for chronic dialysis consumes a substantial portion of healthcare costs for a relatively small proportion of the total population. Each country has a unique reimbursement system that attempts to control rising costs. Thus, comparing the reimbursement systems between countries might be helpful to find solutions to minimize costs to society without jeopardizing quality of treatment and outcomes. We conducted a survey of seven countries to compare crude reimbursement for various dialysis modalities and evaluated additional factors, such as inclusion of drugs or physician payments in the reimbursement package, adjustment in rates for specific patient subgroups, and pay for performance therapeutic thresholds. The comparison examines the United States, the province of Ontario in Canada, and five European countries (Belgium, France, Germany, The Netherlands, and the United Kingdom). Important differences between countries exist, resulting in as much as a 3.3-fold difference between highest and lowest reimbursement rates for chronic hemodialysis. Differences persist even when our data were adjusted for per capita gross domestic product. Reimbursement for peritoneal dialysis is lower in most countries except Germany and the United States. The United Kingdom is the only country that has implemented an incentive if patients use an arteriovenous fistula. Although home hemodialysis (prolonged or daily dialysis) allows greater flexibility and better patient outcomes, reimbursement is only incentivized in The Netherlands. Unfortunately, it is not yet clear that such differences save money or improve quality of care. Future research should focus on directly testing both outcomes.

A preliminary investigation of depression and kidney functioning in patients with chronic kidney disease.

BACKGROUND: The incidence and prevalence of Chronic Kidney Disease (CKD) is growing rapidly. Understanding the factors associated with declining renal function is of clinical significance. The current study's main goal was to identify variables that could predict decline in glomerular filtration rate (GFR) over time in outpatients with varying stages of CKD. METHODS: Seventy CKD patients completed psychological questionnaires and medical variables were extracted from the medical charts. Follow-up GFR was collected 6 months later. CKD patients with elevated depression scores were compared to patients with subclinical depression on medical and psychological variables. RESULTS: Average Beck Depression Inventory (BDI) score was 10.0 ± 7.8, placing the mean below the cut-off for clinical elevation. GFR was significantly different for the two groups (nondepressed, 40.0 ± 11.3 vs. depressed 29.6 ± 8.9; p < 0.05). Similarly, patients with elevated depression scores reported lower quality of life (Short Form 36 Health Survey; p < 0.05) inferior social support (Interpersonal Support Evaluation List; p < 0.05), and worse community integration (Community Integration Questionnaire; p < 0.05). Utilizing a regression, with a model correcting for baseline GFR, the BDI explained 19% of the variance in GFR score (t = -2.0, p < 0.05) for subjects with decreased GFR. CONCLUSIONS: Increased levels of preexisting depression were associated with inferior quality of life, social support and kidney functioning. Depression scores explained a significant amount of variance in GFR scores at 6 months even when corrected for baseline variability. Elevated depression scores are prevalent in CKD populations and further research on the impact of depression interventions is warranted.

Early Experience With Methylprednisolone on SARS-CoV-2 Infection in the African American Population, a Retrospective Analysis.

BACKGROUND: Coronavirus disease-19 (COVID-19) is associated with acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) with high mortality rates. In African American (AA) populations, COVID-19 presentations and outcomes are more severe. NIH and Interim WHO guidelines had suggested against the use of corticosteroids unless in clinical trials until the recent publication of the RECOVERY trial. Here, we analyzed the treatment effect of methylprednisolone on patients with AKI and ARDS during the initial 2 months of COVID-19 and detail the learning effect within our institution. METHODS: Between March 1 and April 30, 2020, 75 AA patients met our inclusion criteria for ARDS and AKI, of which 37 had received corticosteroids. Twenty-eight-day mortality, improvement in PaO2/FiO2 ratio, and renal function were analyzed. The impact of methylprednisolone treatment was assessed with multivariable methods. RESULTS: Survival in the methylprednisolone group reached 51% at 21 days compared to 29% in the non-corticosteroid group (P < .001). Methylprednisolone improved the likelihood of renal function improvement. PaO2/FiO2 ratio in the methylprednisolone group improved by 73% compared to 45% in the non-corticosteroid group (P = .01). Age, gender, BMI, preexisting conditions, and other treatment factors did not show any impact on renal or PaO2/FiO2 ratio improvement. The use of anticoagulants, the month of treatment, and AKI during hospitalization also influenced outcomes. CONCLUSION: In AA COVID-19 positive patients with ARDS and AKI, IV methylprednisolone lowered the incidence of mortality and improved the likelihood of renal and lung function recovery. Further investigation with a randomized control trial of corticosteroids is warranted.

Online measurement of hemodialysis adequacy using effective ionic dialysance of sodium-a review of its principles, applications, benefits, and risks.

Dialysis dose is an important determinant of clinical outcomes in patients with end stage renal disease on maintenance dialysis. In clinical practice dialysis dose is monitored at least monthly by urea clearance based on Urea Kinetic Modeling. Online clearance monitoring using effective ionic dialysance (EID) of sodium (Na+ ) is available on some hemodialysis machines. This paper reviews the background, methodology, additional applications, and potential risks associated with EID. Effective ionic dialysance provides a reliable, real-time, noninvasive, and inexpensive measurement of dialysis dose during an ongoing hemodialysis (HD) session to allow interventions and assess the impact of these changes on clearance. Surveillance of vascular access flow rates can be used to screen for access dysfunction and refer for interventions. There is a concern that EID measurements may cause Na+ loading because of high dialysate Na+ used during these measurements, however, mathematical models, in vitro experiments, and clinical studies in patients on maintenance HD do not show any evidence of Na+ loading during EID measurements. We cannot rule out the possibility of nonosmotic Na+ accumulation in the skin because no published literature exists on this topic as it pertains to clearance measurements based on EID of Na+ .

A hypothesis for mechanism for brain oedema due to glycine.

Death following the use the glycine distension solution in transurethral prostatectomy (TURP) or hysteroscopic surgery has been attributed to the toxic effect of glycine on the brain through the glycine receptors and hyperammonemia, contending that glycine-associated hyponatremia is isosmotic and therefore would not cause brain oedema. Here we propose a hypothesis that the mechanism of brain oedema and death is actually osmotic brain oedema caused by selective diffusion of glycine into the brain while sodium cannot diffuse out of the brain despite favourable concentration gradient because of the absence of sodium transporter on the cerebral capillaries needed for the exit of sodium from the brain. The mechanism for unidirectional diffusion of solutes into the brain in glycine-associated hyponatremia is explained.

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.

Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients.

BACKGROUND: Primary goal of this randomized, double-blind, placebo-controlled crossover study of Renadyl in end-stage renal disease patients was to assess the safety and efficacy of Renadyl measured through improvement in quality of life or reduction in levels of known uremic toxins. Secondary goal was to investigate the effects on several biomarkers of inflammation and oxidative stress. METHODS: Two 2-month treatment periods separated by 2-month washout and crossover, with physical examinations, venous blood testing, and quality of life questionnaires completed at each visit. Data were analyzed with SAS V9.2. RESULTS: 22 subjects (79%) completed the study. Observed trends were as follows (none reaching statistical significance): decline in WBC count (-0.51 × 10(9)/L, P = 0.057) and reductions in levels of C-reactive protein (-8.61 mg/L, P = 0.071) and total indoxyl glucuronide (-0.11 mg%, P = 0.058). No statistically significant changes were observed in other uremic toxin levels or measures of QOL. CONCLUSIONS: Renadyl appeared to be safe to administer to ESRD patients on hemodialysis. Stability in QOL assessment is an encouraging result for a patient cohort in such advanced stage of kidney disease. Efficacy could not be confirmed definitively, primarily due to small sample size and low statistical power-further studies are warranted.

Considerations in the optimal preparation of patients for dialysis.

Every year, more than 110,000 Americans are newly diagnosed with end-stage renal disease and in the overwhelming majority, maintenance dialysis therapy is initiated. However, most patients, having received no predialysis nephrology care or dietary counseling, are inadequately prepared for starting treatment; furthermore, the majority of patients do not have a functioning permanent dialysis access. Annualized mortality in the USA in the first 3 months after starting dialysis treatment is approximately 45%; this high rate is possibly in part due to inadequate preparation for renal replacement therapy. Data from the Dialysis Outcomes and Practice Patterns study suggest that similar challenges exist in many parts of the world. Implementation of strategies that mitigate the risk of adverse consequences when starting dialysis are urgently needed. In this Review we present a step-by-step approach to tackling inadequate patient preparation, which includes identifying individuals with chronic kidney disease (CKD) who are most likely to need dialysis in the future, referring patients for education, timely placement of dialysis access and timely initiation of dialysis therapy. Treatment with dialysis might not be appropriate for some patients with progressive CKD; these individuals can be optimally managed with nondialytic, maximum conservative management.

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

OBJECTIVES: This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. BACKGROUND: Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. METHODS: In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. RESULTS: All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. CONCLUSIONS: Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department.

Cyclosporin induces renal proto-oncogene RNA message and increased transforming growth factor-beta prior to renal fibrosis: Modification by calcium channel blockade in the salt replete rat.

BACKGROUND: Chronic cyclosporin (CsA) administration has been shown to result in the replacement of epithelial cells in the kidney with fibrous tissue. These changes are kidney-specific, as they do not occur in any other organ. RESULTS: Cyclosporin exposure increases c-fos and c-jun mRNA in the rat kidney but not in the liver. Furthermore, chronic CsA exposure causes a further increase in c-fos and c-jun mRNA and increases the renal expression of transforming growth factor-beta (TGF-beta) mRNA. These changes precede the development of fibrosis. The combined insult of ischaemia and CsA resulted in synergistic increases in c-fos, suggesting that CsA recruited a pathway for c-fos activation different from ischaemia. The calcium channel blocker, verapamil, blocked CsA-induced expression of c-fos and c-jun mRNA, and reduced the amount of TGF-beta expression. CONCLUSION: These data are consistent with the notion that CsA induces protooncogenes, which may be, at least partially, responsible for long-term CsA nephrotoxicity.