Impact of Prior Abdominal Procedures on Peritoneal Dialysis Catheter Outcomes: Findings From the North American Peritoneal Dialysis Catheter Registry.

RATIONALE & OBJECTIVE: A history of prior abdominal procedures may influence the likelihood of referral for peritoneal dialysis (PD) catheter insertion. To guide clinical decision making in this population, this study examined the association between prior abdominal procedures and outcomes in patients undergoing PD catheter insertion. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults undergoing their first PD catheter insertion between November 1, 2011, and November 1, 2020, at 11 institutions in Canada and the United States participating in the International Society for Peritoneal Dialysis North American Catheter Registry. EXPOSURE: Prior abdominal procedure(s) defined as any procedure that enters the peritoneal cavity. OUTCOMES: The primary outcome was time to the first of (1) abandonment of the PD catheter or (2) interruption/termination of PD. Secondary outcomes were rates of emergency room visits, hospitalizations, and procedures. ANALYTICAL APPROACH: Cumulative incidence curves were used to describe the risk over time, and an adjusted Cox proportional hazards model was used to estimate the association between the exposure and primary outcome. Models for count data were used to estimate the associations between the exposure and secondary outcomes. RESULTS: Of 855 patients who met the inclusion criteria, 31% had a history of a prior abdominal procedure and 20% experienced at least 1 PD catheter-related complication that led to the primary outcome. Prior abdominal procedures were not associated with an increased risk of the primary outcome (adjusted HR, 1.12; 95% CI, 0.68-1.84). Upper-abdominal procedures were associated with a higher adjusted hazard of the primary outcome, but there was no dose-response relationship concerning the number of procedures. There was no association between prior abdominal procedures and other secondary outcomes. LIMITATIONS: Observational study and cohort limited to a sample of patients believed to be potential candidates for PD catheter insertion. CONCLUSION: A history of prior abdominal procedure(s) does not appear to influence catheter outcomes following PD catheter insertion. Such a history should not be a contraindication to PD. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is a life-saving therapy for individuals with kidney failure that can be done at home. PD requires the placement of a tube, or catheter, into the abdomen to allow the exchange of dialysis fluid during treatment. There is concern that individuals who have undergone prior abdominal procedures and are referred for a catheter might have scarring that could affect catheter function. In some institutions, they might not even be offered PD therapy as an option. In this study, we found that a history of prior abdominal procedures did not increase the risk of PD catheter complications and should not dissuade patients from choosing PD or providers from recommending it.

Trends, Outcomes, and Economic Implications of Peritoneal Dialysis-Associated Peritonitis Hospitalizations: A National Cohort Study.

INTRODUCTION: Peritoneal dialysis-associated peritonitis (PDAP) is a serious complication of peritoneal dialysis, associated with significant morbidity, modality transition, and mortality. Here, we provide an update on the national burden of this significant complication, highlighting trends in demographics, treatment practices, and in-hospital outcomes of PDAP from 2016 to 2020. METHODS: Utilizing a national all-payer dataset of hospitalizations in the USA, we conducted a retrospective cohort study of adult hospitalizations with a primary diagnosis of PDAP from 2016 to 2020. We analyzed demographic, clinical, and hospital-level data, focusing on in-hospital mortality, PD catheter removal, length of stay, and healthcare expenses. Multivariable logistic regression adjusted for demographic and clinical covariates was employed to identify risk factors associated with adverse outcomes. RESULTS: There was a stable burden of annual PDAP admissions from 2016 to 2020. Healthcare expenditures associated with PDAP were high, totaling over USD 75,000 per admission. Additionally, our data suggest geographic inconsistencies in treatment patterns, with treatment at western and teaching hospitals associated with increased rates of catheter removal relative to northeastern and non-teaching centers and a mean cost of nearly USD 55,000 more in Western states compared to Midwest states. 23.2% of episodes resulted in the removal of the PD catheter. Risk factors associated with adverse outcomes included older age, higher Charlson comorbidity index scores, peripheral vascular disease, and the need for vasopressors. CONCLUSION: PDAP is a major cause of mortality among PD patients, and there is a vital need for future studies to examine the impact of hospital location and teaching status on PDAP outcomes, which can inform treatment practices and resource allocation.

Calciphylaxis and Kidney Disease: A Review.

Calciphylaxis is a life-threatening complication most often associated with chronic kidney disease that occurs as a result of the deposition of calcium in dermal and adipose microvasculature. However, this condition may also be seen in patients with acute kidney injury. The high morbidity and mortality rates associated with calciphylaxis highlight the importance to correctly diagnose and treat this condition. However, calciphylaxis remains a diagnosis that may be clinically challenging to make. Here, we review the literature on uremic calciphylaxis with a focus on its pathophysiology, clinical presentation, advances in diagnostic tools, and treatment strategies. We also discuss the unique histopathological features of calciphylaxis and contrast it with those of other forms of general vessel calcification. This review emphasizes the need for multidisciplinary collaboration including nephrology, dermatology, and palliative care to ultimately provide the best possible care to patients with calciphylaxis.

Nintedanib attenuates peritoneal fibrosis by inhibiting mesothelial-to-mesenchymal transition, inflammation and angiogenesis.

Nintedanib, an Food and Drug Administration (FDA) approved multiple tyrosine kinase inhibitor, exhibits an anti-fibrotic effect in lung and kidneys. Its effect on peritoneal fibrosis remains unexplored. In this study, we found that nintedanib administration lessened chlorhexidine gluconate (CG)-induced peritoneal fibrosis and reduced collagen I and fibronectin expression. This coincided with suppressed phosphorylation of platelet-derived growth factor receptor, fibroblast growth factor receptors, vascular endothelial growth factor receptor and Src family kinase. Mechanistically, nintedanib inhibited injury-induced mesothelial-to-mesenchymal transition (MMT), as demonstrated by decreased expression of α-smooth muscle antigen and vimentin and preserved expression of E-cadherin in the CG-injured peritoneum and cultured human peritoneal mesothelial cells exposed to transforming growth factor-ß1. Nintedanib also suppressed expression of Snail and Twist, two transcription factors associated with MMT in vivo and in vitro. Moreover, nintedanib treatment inhibited expression of several cytokines/chemokines, including tumour necrosis factor-α, interleukin-1ß and interleukin-6, monocyte chemoattractant protein-1 and prevented infiltration of macrophages to the injured peritoneum. Finally, nintedanib reduced CG-induced peritoneal vascularization. These data suggest that nintedanib may attenuate peritoneal fibrosis by inhibiting MMT, inflammation, and angiogenesis and have therapeutic potential for the prevention and treatment of peritoneal fibrosis in patients on peritoneal dialysis.

Physical Activity in Kidney Transplant Recipients: A Review.

Physical activity has known health benefits and is associated with reduced cardiovascular risk in the general population. Relatively few data are available for physical activity in kidney transplant recipients. Compared to the general population, physical activity levels are lower overall in kidney recipients, although somewhat higher compared to the dialysis population. Recipient comorbid condition, psychosocial and socioeconomic factors, and long-term immunosuppression use negatively affect physical activity. Physical inactivity in kidney recipients may be associated with reduced quality of life, as well as increased mortality. Interventions such as exercise training appear to be safe in kidney transplant recipients and are associated with improved quality of life and exercise capacity. Additional studies are required to evaluate long-term effects on cardiovascular risk factors and ultimately cardiovascular disease outcomes and patient survival. Currently available data are characterized by wide variability in the interventions and outcome measures investigated in studies, as well as use of small sample-sized cohorts. These limitations highlight the need for larger studies using objective and standardized measures of physical activity and physical fitness in kidney transplant recipients.

High-Output Cardiac Failure and Coronary Steal With an Arteriovenous Fistula.

Creation of an arteriovenous access for hemodialysis can provoke a sequence of events that significantly affects cardiovascular hemodynamics. We present a 78-year-old man with end-stage renal disease and concomitant coronary artery disease previously requiring coronary artery bypass grafting including a left internal mammary graft to the left anterior descending artery, ischemic cardiomyopathy with left ventricular systolic dysfunction, and severe aortic stenosis who developed hypotension unresponsive to medical therapy after recent angioplasty of his ipsilateral arteriovenous fistula for high-grade outflow stenosis. This case highlights the long-term effects of dialysis access on the cardiovascular system, with special emphasis on complications such as high-output cardiac failure and coronary artery steal syndrome. Banding of the arteriovenous fistula provided symptomatic relief with a decrease in cardiac output. Avoidance of arteriovenous access creation on the ipsilateral upper extremity in patients with a left internal mammary artery bypass graft may prevent coronary artery steal syndrome.

Vitamin D and cinacalcet are associated with increased survival in peritoneal dialysis but not with residual renal function preservation
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BACKGROUND: Active vitamin D and cinacalcet, a treatment for secondary hyperparathyroidism and also with potential anti-inflammatory properties, have been associated with lower risk of death among dialysis patients. Vitamin D has also been described to decrease proteinuria in CKD patients. This study aims to assess the relationship of vitamin D and cinacalcet with survival and residual renal function preservation among peritoneal dialysis patients. MATERIALS AND METHODS: In a retrospective peritoneal dialysis cohort of 581 subjects, we assessed if vitamin D and cinacalcet therapy are associated with increased risk of death and residual renal function loss using Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: Vitamin D treatment was associated with a 56% reduction in the risk of death (HR 0.44, 95% CI 0.28 - 0.67) and cinacalcet also with a 54% lower risk of death (HR 0.46, 95% CI 0.31 - 0.69) in multivariate models adjusting for each other. Hyperphosphatemia (> 6 mg/dL) was associated with an 85% increase in mortality (HR 1.85, 95% CI 1.30 - 2.65). Neither vitamin D (HR 1.04, 95% CI 0.45 - 2.39) nor cinacalcet (HR 0.74, 95% CI 0.45 - 1.20) were associated with a lower risk of anuria. CONCLUSION: Vitamin D and cinacalcet therapy was associated with a lower risk of death but not anuria, beyond other known risk factors among peritoneal dialysis patients.
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Residual Renal Function and Obstructive Sleep Apnea in Peritoneal Dialysis: A Pilot Study.

PURPOSE: Obstructive sleep apnea is common in patients with end-stage renal disease, and there is increasing evidence that clinical factors specific to end-stage renal disease contribute pathophysiologically to obstructive sleep apnea. It is not known whether circumstances specific to dialysis modality, in this case peritoneal dialysis, affect obstructive sleep apnea. Our study aimed to investigate the prevalence of obstructive sleep apnea in the peritoneal dialysis population and the relevance of dialysis-specific measures and kidney function in assessing this bidirectional relationship. METHODS: Participants with end-stage renal disease who were treated with nocturnal automated peritoneal dialysis for at least 3 months were recruited from a hospital-based dialysis center. Laboratory measures of dialysis adequacy, peritoneal membrane transporter status, and residual renal function were gathered by chart review. Patients participated in a home sleep apnea test using a level III sleep apnea monitor. RESULTS: Of fifteen participants recruited, 33% had obstructive sleep apnea diagnosed by apnea-hypopnea index ≥ 5 events per hour of sleep. Renal creatinine clearance based upon 24-h urine collection was negatively correlated with apnea-hypopnea index (ρ = - 0.63, p = 0.012). There were no significant associations between anthropometric measures, intra-abdominal dwell volume, or peritoneal membrane transporter status and obstructive sleep apnea measures. CONCLUSIONS: The prevalence of obstructive sleep apnea and sleep disturbances is high in participants receiving peritoneal dialysis. Elevated apnea-hypopnea index is associated with lower residual renal function, whereas dialysis-specific measures such as intra-abdominal dwell volume and peritoneal membrane transporter status do not correlate with severity of obstructive sleep apnea.

Correction to: Residual Renal Function and Obstructive Sleep Apnea in Peritoneal Dialysis: A Pilot Study.

The original version of this article unfortunately contained a mistake in the article title. The correct article title is "Residual Renal Function and Obstructive Sleep Apnea in Peritoneal Dialysis: A Pilot Study".

Renal Mass and Localized Renal Cancer: AUA Guideline.

PURPOSE: This AUA Guideline focuses on evaluation/counseling and management of adult patients with clinically localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions. MATERIALS AND METHODS: Systematic review utilized research from the Agency for Healthcare Research and Quality and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A/B/C (Strong/Moderate/Conditional Recommendations, respectively) with additional statements presented as Clinical Principles or Expert Opinions. RESULTS: Great progress has been made since the previous guidelines on management of localized renal masses were released (2009). The current guidelines provide updated, evidence-based recommendations regarding evaluation/counseling of patients with clinically localized renal masses, including the evolving role of renal mass biopsy. Given great variability of clinical, oncologic and functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Management options (partial nephrectomy/radical nephrectomy/thermal ablation/active surveillance) are reviewed including recent data about comparative effectiveness and potential morbidities. Oncologic issues are prioritized while recognizing that functional outcomes are of great importance for survivorship for most patients with localized kidney cancer. A more restricted role for radical nephrectomy is recommended following well-defined selection criteria. Priority for partial nephrectomy is recommended for clinical T1a lesions, along with selective use of thermal ablation, particularly for tumors ≤3.0 cm. Important considerations for shared decision-making about active surveillance are explicitly defined. CONCLUSIONS: Several factors should be considered during counseling/management of patients with clinically localized renal masses, including general health/comorbidities, oncologic potential of the mass, pertinent functional issues and relative efficacy/potential morbidities of various management strategies.

The Nephrologist's Tumor: Basic Biology and Management of Renal Cell Carcinoma.

Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that is commonly seen in the general practice of nephrology. However, RCC is under-recognized by the nephrology community, such that its presence in curricula and research by this group is lacking. In the most common form of RCC, clear cell renal cell carcinoma (ccRCC), inactivation of the von Hippel-Lindau tumor suppressor is nearly universal; thus, the biology of ccRCC is characterized by activation of hypoxia-relevant pathways that lead to the associated paraneoplastic syndromes. Therefore, RCC is labeled the internist's tumor. In light of this characterization and multiple other metabolic abnormalities recently associated with ccRCC, it can now be viewed as a metabolic disease. In this review, we discuss the basic biology, pathology, and approaches for treatment of RCC. It is important to distinguish between kidney confinement and distant spread of RCC, because this difference affects diagnostic and therapeutic approaches and patient survival, and it is important to recognize the key interplay between RCC, RCC therapy, and CKD. Better understanding of all aspects of this disease will lead to optimal patient care and more recognition of an increasingly prevalent nephrologic disease, which we now appropriately label the nephrologist's tumor.

Preserving residual renal function in dialysis: what we know.

Residual renal function confers a survival benefit among dialysis patients thought to be related to greater volume removal and solute clearance. Whether the presence of residual renal function is protective or merely a marker for better health is not clear. The basic mechanisms governing the decline or persistence of residual renal function are poorly understood and few studies have examined the role of medical therapy in its preservation. Dialysis modality, inflammatory processes often associated with comorbid diseases (including diabetes mellitus and obesity), volume dysregulation, and vitamin D deficiency are predictive of residual renal function decline. We review potential mechanisms for preservation of remaining glomerular filtration rate among chronic dialysis patients.

The Association of Intra-Abdominal Adhesions with Peritoneal Dialysis Catheter-Related Complications.

BACKGROUND: This study investigated the association of intra-abdominal adhesions with the risk of peritoneal dialysis (PD) catheter complications. METHODS: Individuals undergoing laparoscopic PD catheter insertion were prospectively enrolled from eight centers in Canada and the United States. Patients were grouped based on the presence of adhesions observed during catheter insertion. The primary outcome was the composite of PD never starting, termination of PD, or the need for an invasive procedure caused by flow restriction or abdominal pain. RESULTS: Seven hundred and fifty-eight individuals were enrolled, of whom 201 (27%) had adhesions during laparoscopic PD catheter insertion. The risk of the primary outcome occurred in 35 (17%) in the adhesion group compared with 58 (10%) in the no adhesion group (adjusted HR, 1.64; 95% confidence interval [CI], 1.05 to 2.55) within 6 months of insertion. Lower abdominal or pelvic adhesions had an adjusted HR of 1.80 (95% CI, 1.09 to 2.98) compared with the no adhesion group. Invasive procedures were required in 26 (13%) and 47 (8%) of the adhesion and no adhesion groups, respectively (unadjusted HR, 1.60: 95% CI, 1.04 to 2.47) within 6 months of insertion. The adjusted odds ratio for adhesions for women was 1.65 (95% CI, 1.12 to 2.41), for body mass index per 5 kg/m 2 was 1.16 (95% CI, 1.003 to 1.34), and for prior abdominal surgery was 8.34 (95% CI, 5.5 to 12.34). Common abnormalities found during invasive procedures included PD catheter tip migration, occlusion of the lumen with fibrin, omental wrapping, adherence to the bowel, and the development of new adhesions. CONCLUSIONS: People with intra-abdominal adhesions undergoing PD catheter insertion were at higher risk for abdominal pain or flow restriction preventing PD from starting, PD termination, or requiring an invasive procedure. However, most patients, with or without adhesions, did not experience complications, and most complications did not lead to the termination of PD therapy.

The impact of anemia on renal recovery and survival in acute kidney injury.

BACKGROUND: Anemia occurs frequently among patients who develop acute kidney injury likely due to abnormal erythropoietic activity. Anemia has been associated with increased mortality among hospitalized patients, but its impact on renal recovery or survival is poorly characterized among patients with acute kidney injury. We aim to assess if anemia is associated with lower renal recovery and poorer survival. METHODS: A retrospective cohort of 211 patients was examined. Anemia and other patient characteristics were assessed as potential risk factors for the presence of renal recovery or death. Additionally, renal recovery, dialysis requirement and survival were compared between those with mild versus severe anemia. RESULTS: 86% of patients with acute kidney injury (AKI) developed acute anemia which generally occurred at the time of acute kidney injury. Anemia did not appear to be associated with lack of renal recovery or death, but rather underlying comorbid conditions and severity of illness were more likely to be associated with renal recovery or death, respectively. Neither renal recovery nor survival differed among patients with mild versus severe anemia as measured by fall in hemoglobin or nadir hemoglobin. CONCLUSIONS: New onset anemia does not appear to be associated with lack of renal recovery or death among patients with acute kidney injury.

The role of graft-versus-host disease in haematopoietic cell transplantation-associated glomerular disease.

BACKGROUND: Glomerular disease among haematopoietic cell transplantation recipients has been attributed to chronic graft-versus-host disease. Clinical outcomes of this population may be influenced by the haematopoietic cell transplantation conditioning regimen, donor factors and chronic graft-versus-host disease. METHODS: In this review, 95 cases of haematopoietic cell transplantation-associated glomerular disease were identified from literature review for analysis. Patient characteristics, the association of chronic graft-versus-host disease with glomerular diseases, and the impact of host and haematopoietic cell transplantation regimen on outcomes were evaluated. RESULTS: The median onset of glomerular disease from haematopoietic cell transplantation and from cessation of immunosuppressive agents was 15.5 and 1 month, respectively. Although chronic graft-versus-host disease was common among haematopoietic cell transplant recipients with glomerulonephritis (72%), this was no different from that observed in the overall haematopoietic cell transplantation population. Membranous nephropathy and minimal change disease are the most prevalent glomerular diseases among haematopoietic cell transplantation recipients. Chronic graft-versus-host disease, donor factors and haematopoietic cell transplant regimen did not significantly impact outcomes in this study population. CONCLUSIONS: Pathogenic mechanisms in addition to (or other than) chronic graft-versus-host disease are likely contribute to haematopoietic cell transplantation-associated glomerular disease. Further investigation will be required to delineate clearly the pathogenesis.

Periprocedural Peritonitis Prophylaxis: A Summary of the Microbiology and the Role of Systemic Antimicrobials.

BACKGROUND: Peritonitis is a leading complication of peritoneal dialysis (PD). One strategy that the International Society for Peritoneal Dialysis (ISPD) has used to help mitigate the morbidity and mortality associated with peritonitis is through prevention, including antibiotic prophylaxis utilization in high-risk situations. The aim of this study is to summarize our current understanding of postprocedural peritonitis and discuss the existing data behind periprocedural antibiotic prophylaxis, focusing primarily on PD catheter insertion, dental procedures, colonoscopies, upper endoscopies with gastrostomy, and gynecologic procedures. SUMMARY: The ISPD currently recommends intravenous antibiotics prior to PD catheter insertion, colonoscopies, and invasive gynecologic procedures, though prophylaxis has only demonstrated benefit in a prospective, randomized control setting for PD catheter insertion. However, multiple retrospective studies exist that support the use of antibiotic prophylaxis for the other 2 procedures. No specific antibiotic regimen has been established as most optimal to prevent peritonitis for any of the 3 procedures. Antibiotic coverage should include the Enterobacteriaceae family, as well as Gram-positive organisms commonly found on the skin flora for PD catheter insertion, anaerobes for colonoscopies, and common organisms from the urogenital flora in gynecologic procedures. Additionally, the ISPD currently recommends oral amoxicillin prior to dental procedures. There is currently no ISPD recommendation to provide antibiotic prophylaxis prior to an upper endoscopy with or without gastrostomy, though this is a potential area for research. KEY MESSAGES: PD patients are at high risk for developing peritonitis after typical procedures. Antibiotic prophylaxis is a potential strategy that the ISPD utilizes to prevent these infections. However, further research needs to be done to determine the optimal antibiotic regimen.

Glomerulonephritis after hematopoietic cell transplantation: IgA nephropathy with increased excretion of galactose-deficient IgA1.

We report the development of IgA nephropathy (IgAN) following full myeloablative allogeneic hematopoietic cell transplantation in two patients with human leukocyte antigen (HLA) matched sibling donors, unrelated to active or chronic graft-versus-host disease. Both recipients had elevated urinary levels of galactose-deficient IgA1, and one donor-recipient pair had elevated serum levels of galactose-deficient IgA1. We propose that IgAN developed after bone marrow transplantation due to a non-graft-versus-host-disease-related multi-hit process associated with glomerular deposition of galactose-deficient IgA1. These two cases provide unique insight into the kinetics of overproduction of galactose-deficient IgA1 and its glomerular deposition and consequential renal injury in IgAN.

The Nephrologist's Management of Renal Cell Carcinoma After Kidney Surgery.

Renal cell carcinoma is associated with chronic kidney disease as well as with common risk factors including hypertension and diabetes mellitus. Localized renal cell carcinoma is treated surgically and in these cases has a favorable prognosis. In particular, in those individuals with small renal masses (≤4 cm), preservation of kidney function should be prioritized. Postoperative chronic kidney disease or end-stage renal disease prevention should include baseline kidney function and risk factor assessment, nontumor renal biopsy, as well as counseling on treatment options to discuss maximizing kidney function preservation. Postnephrectomy prognosis can be determined with repeat laboratory and clinical assessment. Ultimately, early involvement of the nephrologist in a multidisciplinary team including the urology team will enable the reduction of postsurgical kidney disease related morbidity and potentially mortality.

Ochrobactrum Peritonitis: Case Report and Literature Review.

End-stage kidney disease (ESKD) patients, including those on peritoneal dialysis (PD), are considered immunocompromised and at risk for opportunistic pathogens. Peritonitis is a major infectious PD complication with common causative pathogens, including gram-positive organisms such as coagulase-negative Staphylococcus species, Staphylococcus aureus more often than gram negative organisms. PD peritonitis is often secondary to suboptimal technique leading to contamination of the catheter site but can also be due to bacterial translocation from the bowel lumen or transient bacteremia after procedures; this makes identification of the causative organism crucial to optimal management of PD peritonitis. Ochrobactrum are glucose-non-fermentative, non-fastidious, motile gram-negative bacilli typically isolated in aqueous environments. Reported infections primarily occur in immunocompromised hosts with environmental exposure, including nosocomial contamination of fluids or indwelling catheters. We present only the seventh reported case of Ochrobactrum peritonitis in a 67-year-old PD patient secondary to poor technique, and review the literature for all prior cases. Although there have been no previous cases leading to bacteremia, three of the seven cases required removal of PD catheter.

Reliability of urinalysis for identification of proteinuria is reduced in the presence of other abnormalities including high specific gravity and hematuria.

PURPOSE: Chronic kidney disease (CKD) is classified according to cause, glomerular filtration rate, and proteinuria. Identification of proteinuria with urinalysis (UA) is less accurate than quantification via other methods. We investigated factors leading to discordant UA findings when compared against paired albumin-to-creatinine ratio (ACR) testing. METHODS: Four thousand three hundred and twenty-three UAs were grouped by proteinuria level (A1-A3); concordance with ACR was examined. Classification of UA with confounding factors (UA+CF) or without (UA-CF) was based on CF that resulted in >10% increase in false-positive proteinuria readings. The presence of ≥3+ blood, ≥3+ leukocyte esterase, any ketonuria, specific gravity ≥1.020, ≥1+ urobilinogen, ≥2+ bilirubin, ≥2+ bacteria, ≥3 RBC/hpf (high powered field), ≥10 WBC/hpf, and/or ≥6 epithelial cells/hpf led to UA+CF classification. RESULTS: Proteinuria was determined to be present in 14.1% by UA dipstick and 24.9% by ACR. Using ACR as the standard, overall concordance was 80.4%, with 17.2% false-negatives and 2.3% false-positives by UA. UA+CF represented 55.6% of UA overall (n = 2404), and 98.0% of those false-positive for proteinuria. High specific gravity and hematuria are the strongest predictors of false positives. For A2 proteinuria (30-300 mg/g, 1+,2+,3+ on UA) UA-CF had a higher negative predictive value (NPV) (99.8%) than UA+CF (77.6%); NPV for A3 proteinuria (>300 mg/g, 4+ on UA) was 100% for UA-CF and UA+CF. CONCLUSION: Additional abnormalities were noted in >50% of outpatient UAs indicating proteinuria. Given the significant proportion of patients having a false-positive UA for proteinuria when these CFs were present, we recommend that such patients undergo ACR confirmatory testing, according to a clinical algorithm for the incorporation of UA results into the management of CKD.