APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis.

The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endothelial-specific expression of RV APOL1 and in vitro studies demonstrated that RV APOL1 interfered with mitophagy, leading to cytosolic release of mitochondrial DNA and activation of the inflammasome (NLRP3) and the cytosolic nucleotide sensing pathways (STING). Genetic deletion or pharmacological inhibition of NLRP3 and STING protected mice from RV APOL1-induced permeability defects and proinflammatory endothelial changes in sepsis. Our studies identify the inflammasome and STING pathways as potential targets to reduce APOL1-associated health disparities in sepsis and COVID-19.

Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Predictors and Adverse Outcomes of Acute Kidney Injury in Hospitalized Renal Transplant Recipients.

Data about in-hospital AKI in RTRs is lacking. We conducted a retrospective study of 292 RTRs, with 807 hospital admissions, to reveal predictors and outcomes of AKI during admission. In-hospital AKI developed in 149 patients (51%). AKI in a previous admission was associated with a more than twofold increased risk of AKI in subsequent admissions (OR 2.13, p < 0.001). Other major significant predictors for in-hospital AKI included an infection as the major admission diagnosis (OR 2.93, p = 0.015), a medical history of hypertension (OR 1.91, p = 0.027), minimum systolic blood pressure (OR 0.98, p = 0.002), maximum tacrolimus trough level (OR 1.08, p = 0.005), hemoglobin level (OR 0.9, p = 0.016) and albumin level (OR 0.51, p = 0.025) during admission. Compared to admissions with no AKI, admissions with AKI were associated with longer length of stay (median time of 3.83 vs. 7.01 days, p < 0.001). In-hospital AKI was associated with higher rates of mortality during admission, almost doubled odds for rehospitalization within 90 days from discharge and increased the risk of overall mortality in multivariable mixed effect models. In-hospital AKI is common and is associated with poor short- and long-term outcomes. Strategies to prevent AKI during admission in RTRs should be implemented to reduce re-admission rates and improve patient survival.

The Prognostic Value of Anti-PLA2R Antibodies Levels in Primary Membranous Nephropathy.

Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50-71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35-183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year (p = 0.017, p = 0.003 and p = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment (p = 0.003 and p = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients.

Treatment of Severe Renal Artery Stenosis with Acute Kidney Injury Requiring Hemodialysis by Percutaneous Transluminal Renal Angioplasty and Stent Implantation.

PURPOSE: To evaluate the outcomes of percutaneous transluminal renal angioplasty with stent implantation (PTRAS) among patients with renal artery stenosis (RAS) who become dialysis-dependent due to acute deterioration of renal function. MATERIALS AND METHODS: This was a single-center retrospective cohort study of all PTRAS procedures performed from 2003 to 2019 in a referral hospital. A total of 109 procedures were performed in 92 patients. Eleven patients (12%) presented with anuric acute kidney injury (AKI) secondary to high-grade RAS (defined as intraluminal stenosis above 70% per angiography) and underwent PTRAS after starting hemodialysis. Data collected included demographic parameters, medical background, creatinine, blood pressure, indication for intervention, procedure characteristics, adverse events, and long-term data including dialysis treatment and mortality. Among the dialysis-dependent AKI group, outcome measures were defined based on the postprocedural improvement in kidney function and discontinuation of dialysis. RESULTS: Following PTRAS, 8 of 11 patients (73%) demonstrated improved kidney function and were able to discontinue dialysis. The median time on dialysis was 18 days (range, 2-35 days) before PTRAS and 4.5 days (range, 1-24 days) to recovery of kidney function after the time of intervention. CONCLUSIONS: Patients with atherosclerotic RAS who develop RAS-related AKI may benefit from PTRAS even after several weeks of anuria and dialysis dependence.

A multidisciplinary nephrogenetic referral clinic for children and adults-diagnostic achievements and insights.

BACKGROUND: Genetic kidney diseases contribute a significant portion of kidney diseases in children and young adults. Nephrogenetics is a rapidly evolving subspecialty; however, in the clinical setting, increased use of genetic testing poses implementation challenges. Consequently, we established a national nephrogenetics clinic to apply a multidisciplinary model. METHODS: Patients were referred from different pediatric or adult nephrology units across the country if their primary nephrologist suspected an undiagnosed genetic kidney disease. We determined the diagnostic rate and observed the effect of diagnosis on medical care. We also discuss the requirements of a nephrogenetics clinic in terms of logistics, recommended indications for referral, and building a multidisciplinary team. RESULTS: Over 24 months, genetic evaluation was completed for a total of 74 unrelated probands, with an age range of 10 days to 72 years. The most common phenotypes included congenital anomalies of the kidneys and urinary tract, nephrotic syndrome or unexplained proteinuria, nephrocalcinosis/nephrolithiasis, tubulopathies, and unexplained kidney failure. Over 80% of patients were referred due to clinical suspicion of an undetermined underlying genetic diagnosis. A molecular diagnosis was reached in 42/74 probands, yielding a diagnostic rate of 57%. Of these, over 71% of diagnoses were made via next generation sequencing (gene panel or exome sequencing). CONCLUSIONS: We identified a substantial fraction of genetic kidney etiologies among previously undiagnosed individuals which influenced subsequent clinical management. Our results support that nephrogenetics, a rapidly evolving field, may benefit from well-defined multidisciplinary co-management administered by a designated team of nephrologist, geneticist, and bioinformatician. A higher resolution version of the Graphical abstract is available as Supplementary information.

Amyloid storm: acute kidney injury and massive proteinuria, rapidly progressing to end-stage kidney disease in AA amyloidosis of familial Mediterranean fever.

OBJECTIVE: Amyloid A nephropathy of FMF usually progresses over many years to end-stage renal disease (ESRD). We aim to describe an acute condition, termed here 'amyloid storm', typically manifesting with a rapid (≤2 weeks) increase in serum creatinine and urine protein, that has never been characterized in FMF amyloidosis. METHODS: This retrospective analysis features amyloid storm by comparing between FMF amyloidosis patients who have experienced an episode of amyloid storm (study group) and matched patients who have not (control group). The primary outcome was ESRD or death within 1 year from study entry. Featured data were retrieved from hospital files. RESULTS: The study and control groups, each comprising 20 patients, shared most baseline characteristics. However, they differed on the time from FMF onset to reaching serum creatinine of 1.2 mg/dl [26.5 years (s.d. 15.15) vs 41.55 (10.98), P = 0.001] and the time from the onset of proteinuria to study entry [8.8 years (s.d. 6.83) vs 15.75 (13.05), P = 0.04], culminating in younger age at study entry [39.95 years (s.d. 16.81) vs 48.9 (9.98), respectively, P = 0.05] and suggesting an accelerated progression of kidney disease in the study group. Within 1 year from study entry, 16 patients in the study and 3 in the control groups reached the primary endpoint (P = 0.000). The major triggers of amyloid storm were infections, occurring in 17 of 20 patients. CONCLUSION: Amyloid storm is a complication of FMF amyloidosis, induced by infection and associated with poor prognosis and death.

Regular at-home abdominal paracentesis via Tenckhoff catheter in patients with refractory congestive heart failure.

BACKGROUND: Peritoneal dialysis (PD) is increasingly used for the long-term management of refractory congestive heart failure (CHF). Patients with severe CHF and ascites were treated with regular at-home abdominal paracentesis via Tenckhoff catheter. We investigated the outcome of those patients, aiming to identify potential prognostic factors for longer survival. METHODS: Patients with refractory CHF referred by cardiologists to the PD unit from years 2009 to 2019 and treated with regular at-home abdominal paracentesis via Tenckhoff catheter without peritoneal exchanges, were enrolled into this prospective observational study. RESULTS: From the total of 69 refractory CHF patients treated with PD, 18 (26%) were managed with regular at-home abdominal paracentesis via Tenckhoff catheter and improved without the need for peritoneal exchanges for fluid removal (no peripheral oedema or pulmonary congestion) or for solutes removal. Median survival of severe CHF patients treated with abdominal paracentesis was 13.5 months (0-34 months). Long-term survivors demonstrated significant improvement in the New York Heart Association (NYHA) functional class, improvement in kidney function and decrease in serum C-reactive protein (CRP) and Brain natriuretic peptide (BNP) compared with their baseline status. A subgroup of patients with shorter survival were more likely to have evidence of liver cirrhosis and significantly lower serum sodium compared with patients with longer survival. CONCLUSIONS: Refractory CHF patients with massive ascites could be successfully treated with regular at-home abdominal paracentesis via Tenckhoff catheter. This treatment provides a useful alternative to periodical percutaneous paracentesis on as-needed basis.

Congestive heart failure treated with peritoneal dialysis or hemodialysis: Typical patient profile and outcomes in real-world setting.

BACKGROUND: Peritoneal dialysis (PD) is increasingly used for the long-term management of hypervolemic refractory congestive heart failure (CHF) patients, in particular when complicated by renal insufficiency. While PD has many advantages over hemodialysis (HD) in those patients, there is a controversy concerning survival superiority of PD compared with HD in this population. The aim of the study was to define typical patient profile and to compare outcomes of patients with CHF and renal failure treated with HD or PD. METHODS: This retrospective cohort study enrolled CHF patients treated with chronic PD or HD between the years 2009-2018. Information at dialysis initiation included age, gender, body weight, blood pressure, cause of renal disease, comorbidities, hospitalisations, echocardiographic and laboratory parameters. Survival was compared between PD and HD patients using a Kaplan-Meier model and Cox regression analysis. RESULTS: CHF patients treated with PD had significantly higher eGFR and lower systolic blood pressure compared with HD treated patients. Median survival time was 13.32 (7.08, 23.28) months in the PD group and 19.68 (9.48, 39.24) months in the HD group, P = .013. After adjustment for confounders the mortality risk amongst PD and HD patients was not significantly different: adjusted HR for death in PD vs HD patients was 1.44, P = .35 for 1- year and 1.69, P = .10 for 2-year mortality. Number of hospitalisations was similar in both groups. CONCLUSIONS: CHF patient profile was different in PD and HD. Two modalities were equally effective in the treatment of patients with CHF and renal failure considering different patient characteristics.

[TREATMENT OF SEVERE ATHEROSCLEROTIC RENAL ARTERY STENOSIS WITH ACUTE KIDNEY INJURY REQUIRING HEMODIALYSIS BY PERCUTANEOUS TRANSLUMINAL RENAL ANGIOPLASTY AND STENT IMPLANTATION].

INTRODUCTION: Treatment of atherosclerotic renal artery stenosis (RAS) is still controversial. Several randomized controlled trials have shown that percutaneous transluminal renal angioplasty with stenting (PTRAS) is not superior to medical treatment, and the procedure is commonly reserved for malignant hypertension, flash pulmonary edema or deterioration of kidney function. The most challenging symptomatic RAS cases are patients with severe stenosis resulting in acute kidney injury (AKI) requiring acute hemodialysis. The risk-benefit ratio in these cases is uncertain. While those patients might benefit the most from revascularization, the success rate after prolonged time on dialysis is unknown. This is a representative case study of a patient with solitary kidney and high grade RAS who presented with anuric AKI indicated for hemodialysis. Twenty-eight days after starting hemodialysis the patient underwent PTRAS as a rescue therapy and 5 days after the procedure urine output resumed, the patient became polyuric and kidney function improved and the patient stopped hemodialysis.

Early persistent hyperparathyroidism post-renal transplantation as a predictor of worse graft function and mortality after transplantation.

BACKGROUND: Persistent hyperparathyroidism (pHPT) is frequently seen after transplantation contributing to post-transplant complications. METHODS: We conducted a retrospective single center analysis to explore the relationship of early pHPT and long-term allograft outcome. Patients were divided into high (N = 153) and low (N = 252) PTH groups based on serum parathyroid hormone (PTH) level 3 months post-transplant (PTH ≥ 150 and < 150 pg/mL, respectively). RESULTS: High PTH was found to be an independent predictor for reduced kidney allograft function up to 3 years post-transplant. eGFR decreased by 11.4 mL/min (P < .001) and the odds of having an eGFR < 60 mL/min 3 years post-transplant were sixfold higher (P < .01) in the high compared to the low PTH group. Subgroup analysis based on eGFR 1 year post-transplant, presence of slow graft function (SGF), and transplant type revealed similar results. High PTH three months post-transplant was also independently associated with an increased risk for overall mortality and for death with a functioning graft (P < .05). CONCLUSIONS: pHPT three months post-renal transplantation is an independent predictor for a worse allograft function up to 3 years post-transplant and a risk factor for mortality. This relationship remains statistically significant after accounting for baseline allograft function, presence of SGF and serum mineral levels abnormalities.

Effect of Peritoneal Dialysis on Serum Fibrosis Biomarkers in Patients with Refractory Congestive Heart Failure.

BACKGROUND: Cardiac collagen remodeling is important in the progression of heart failure. Estimation of cardiac collagen turnover by serum levels of serological markers is used for monitoring cardiac tissue repair and fibrosis. Peritoneal dialysis (PD) is used for the long-term management of refractory congestive heart failure (CHF). In this study, we investigated the effect of PD treatment on circulating fibrosis markers levels in patients with refractory CHF and fluid overload. METHODS: Twenty-five patients with refractory CHF treated with PD were prospectively enrolled in the study. Circulating fibrosis markers procollagen type III C-peptide (PIIINP), matrix metalloproteinase 2 (MMP-2), and tissue inhibitor of metalloproteinases I (TIMP-1) levels were checked at baseline and after three and six months of treatment. RESULTS: The clinical benefit of PD manifested by improved NYHA functional class and reduced hospitalization rate. Serum brain natriuretic peptide (BNP) levels decreased significantly during the treatment. Serum MMP-2 and TIMP-1 decreased significantly on PD. Circulating PIIINP showed two patterns of change, either decreased or increased following PD treatment. Patients in whom circulating PIIINP decreased had significantly lower baseline serum albumin, lower baseline mean arterial blood pressure, higher serum CRP, and a less significant improvement in hospitalization rate compared to the patients in whom circulating PIIINP increased. Patients in whom all three markers decreased demonstrated a trend to longer survival compared to patients whose markers increased or did not change. CONCLUSION: In refractory CHF patients PD treatment was associated with a reduction in circulating fibrosis markers.

Epigenetics: a new way to look at kidney diseases.

Only a few percent of the 3 billion pairs of chemical letters in the human genome is responsible for protein-coding sequences. Recent advances in the field of epigenomics have helped us to understand how most of the remaining sequences are responsible for gene regulation at baseline and in disease conditions. Here we discuss recent advances in the area of epigenetics--specifically in cytosine modifications--and its application in the field of nephrology.

Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression.

BACKGROUND: Chronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us the chronological age and predict multiple health-related outcomes. However, why some sites correlating with lifespan, healthspan, or specific medical conditions remain poorly understood. Kidney fibrosis is the common pathway for chronic kidney disease, which affects 10% of European and US populations. RESULTS: Here we identify epigenetic clocks and methylation sites that correlate with kidney function. Moreover, we identify methylation sites that have a unique methylation signature in the kidney. Methylation levels in majority of these sites correlate with kidney state and function. When kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Interestingly, while the majority of sites are less methylated in the kidney and become more methylated with loss of function, a fraction of the sites are highly methylated in the kidney and become less methylated when kidney function declines. These methylation sites are enriched for specific transcription-factor binding sites. In a large subset of sites, changes in methylation patterns are accompanied by changes in gene expression in kidneys of chronic kidney disease patients. CONCLUSIONS: These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines. However, this information loss is not random, but guided toward a baseline that is dependent on the genomic loci. SIGNIFICANCE STATEMENT: DNA methylation at specific sites accurately reflects chronological and biological age. We identify sites that have a unique methylation pattern in the kidney. Methylation levels in the majority of these sites correlate with kidney state and function. Moreover, when kidney function deteriorates, all of these sites regress toward the common methylation pattern observed in other tissues. Thus, the unique methylation signature of the kidney is degraded, and epigenetic information is lost, when kidney disease progresses. These methylation sites are enriched for specific and methylation-sensitive transcription-factor binding sites, and associated genes show disease-dependent changes in expression. These results support the information theory of aging, and the hypothesis that the unique tissue identity, as captured by methylation patterns, is lost as tissue function declines.

Physical fitness is an independent predictor of chronic kidney disease development in apparently healthy individuals.

BACKGROUND: The cardiovascular and metabolic benefits of physical activity have been studied at length, however, data on the association between physical fitness and progression to kidney disease is lacking. We aimed to identify the association between cardiorespiratory fitness and development of chronic kidney disease (CKD) among the healthy population. METHODS: We retrospectively investigated 11,579 healthy self-referred subjects who underwent annual medical screening. All subjects had an estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73 m2, no known kidney disease, hematuria or proteinuria, and were free of diabetes or cardiovascular disease at baseline. All participants completed a maximal exercise test, and were categorized into low and high cardiorespiratory fitness groups based on age- and gender-specific quintiles. The primary end point was the development of significant CKD defined as eGFR below 45 ml/min/1.73 m2 during follow-up. RESULTS: Median follow-up was 7.6 years, and the participants' median age was 50 ± 8 years. Baseline creatinine and eGFR were 1.02 mg/dl and 81 ml/min/1.73 m2, respectively. During follow-up, 81 (0.6%) participants developed CKD, and the cumulative probability was significantly higher among the low fitness group (HR = 2.41, p = 0.001). The effect of physical fitness on the risk to develop CKD remained significant after adjusting for age, gender, baseline creatinine and other cardiovascular risk factors. CONCLUSION: Cardiorespiratory fitness is an independent risk factor inversely associated with development of CKD.

The ERA Registry Annual Report 2021: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD). This paper is a summary of the ERA Registry Annual Report 2021, including a comparison across treatment modalities. Methods: Data was collected from 54 national and regional registries from 36 countries, of which 35 registries from 18 countries contributed individual patient data and 19 registries from 19 countries contributed aggregated data. Using this data, incidence and prevalence of KRT, kidney transplantation rates, survival probabilities and expected remaining lifetimes were calculated. Result: In 2021, 533.2 million people in the general population were covered by the ERA Registry. The incidence of KRT was 145 per million population (pmp). In incident patients, 55% were 65 years or older, 64% were male, and the most common primary renal disease (PRD) was diabetes (22%). The prevalence of KRT was 1040 pmp. In prevalent patients, 47% were 65 years or older, 62% were male, and the most common PRDs were diabetes and glomerulonephritis/sclerosis (both 16%). On 31 December 2021, 56% of patients received haemodialysis, 5% received peritoneal dialysis, and 39% were living with a functioning graft. The kidney transplantation rate in 2021 was 37 pmp, a majority coming from deceased donors (66%). For patients initiating KRT between 2012-2016, 5-year survival probability was 52%. Compared to the general population, life expectancy was 65% and 68% shorter for males and females receiving dialysis, and 40% and 43% shorter for males and females living with a functioning graft.

Loss-of-function mutations of CYP24A1, the vitamin D 24-hydroxylase gene, cause long-standing hypercalciuric nephrolithiasis and nephrocalcinosis.

PURPOSE: Hypercalciuria is the most common cause of kidney stone disease and genetic factors have an important role in nearly half of these cases. Recently loss-of-function mutations of CYP24A1, the gene encoding vitamin D 24-hydroxylase, were identified in idiopathic infantile hypercalcemia. We describe the clinical and molecular basis of severe long-standing kidney stone disease in adults caused by CYP24A1 mutations. MATERIALS AND METHODS: Three subjects from 2 Israeli families with nephrolithiasis and nephrocalcinosis were clinically characterized. Genomic DNA was isolated from peripheral blood and sequencing of CYP24A1 was performed. RESULTS: All subjects presented with severe kidney stone disease, the cause of which was not discovered for decades despite extensive evaluation. They all had hypercalciuria, nephrocalcinosis and intermittent hypercalcemia, and chronic kidney insufficiency developed in the oldest subject. All patients had a typical pattern of test results, including normal-high serum calcium, low parathyroid hormone levels, high vitamin D 25-(OH)D3 and 1,25-(OH)2D3, and low 24,25-(OH)2D3. Overall 3 CYP24A1 loss-of-function mutations were identified, including a homozygous deletion (delE143) in consanguinous family 1, and compound heterozygous mutations L409S and the novel W268-stop in family 2. CONCLUSIONS: Loss-of-function mutations of CYP24A1 gene, encoding for 1,25-dihydroxyvitamin D3 24-hydroxylase, cause severe hypercalciuric nephrolithiasis and nephrocalcinosis. The mutations may present in adults and may lead to chronic renal insufficiency. Our results support a recessive mode of inheritance. CYP24A1 mutations should be considered in the differential diagnosis of hypercalciuric nephrolithiasis, especially as many adults are now prescribed supplemental oral vitamin D.

Optimal peritoneal fluid white blood cell count for diagnosis of peritonitis in peritoneal dialysis patients.

BACKGROUND: The diagnosis of peritonitis among peritoneal dialysis (PD) patients is based on clinical presentation, dialysis effluent white blood cell (WBC) count, and dialysis effluent culture. Peritoneal fluid WBC count is very important in the initial diagnosis of peritonitis. The purpose of this work was to determine the optimal number of peritoneal WBCs with different clinical presentations at admission to define PD-related peritonitis. METHODS: Medical records of chronic PD patients who underwent work-up for suspected peritonitis between 2008 and 2019 were reviewed retrospectively. Results of all peritoneal WBC count tests during this period were collected. Clinical manifestations and follow-up analysis of each peritoneal WBC count were performed. RESULTS: The peritoneal WBC count cutoff of 100/µL recommended by International Society for Peritoneal Dialysis provided specificity of only 35%. Increasing peritoneal WBC count cutoff to 150, 200, and 250/µL provided sensitivity around 98% and gradually increasing specificity. The chi-square automatic interaction detector model of statistical analysis determined that peritoneal WBC count below 230/µL combined with absence of inflammatory markers (fever, increased C-reactive protein) ruled out peritonitis with 99.8% sensitivity. Peritoneal fluid WBC count cutoff of 230/µL provided specificity of 89% and good positive and negative likelihood scores of 8.3 and 0.03, respectively. Peritoneal fluid polymorphonuclear count has lower discriminating ability for peritonitis compared to peritoneal fluid WBC count. CONCLUSION: Increasing peritoneal fluid WBC count cutoff to 230/µL in suspected PD-related peritonitis could improve specificity without compromising the sensitivity of the test.