Urinary calprotectin, NGAL, and KIM-1 in the differentiation of primarily inflammatory vs. non-inflammatory stable chronic kidney diseases.

INTRODUCTION: It has been demonstrated that urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin are helpful biomarkers in the differentiation of intrinsic and prerenal acute kidney injury. OBJECTIVE: The present cross-sectional study investigates, whether urinary biomarkers are able to differentiate primarily inflammatory from non-inflammatory entities in chronic kidney disease (CKD). METHODS: Urinary calprotectin, NGAL, and kidney injury molecule-1 (KIM-1) concentrations were assessed in a study population of 143 patients with stable CKD and 29 healthy controls. Stable renal function was defined as an eGFR fluctuation ≤5 ml/min/1.73 m2 in the past 12 months. Pyuria, metastatic carcinoma, and renal transplantation were regarded as exclusion criteria. Diabetic nephropathy, hypertensive nephropathy, and polycystic kidney disease were categorized as 'primarily non-inflammatory renal diseases' (NIRD), whereas glomerulonephritis and vasculitis were regarded as 'primarily inflammatory renal diseases' (IRD). RESULTS: Urinary calprotectin and NGAL concentrations significantly differed between CKD and healthy controls (p < 0.05 each), whereas KIM-1 concentrations did not (p = 0.84). The three biomarkers did neither show significant differences in-between the individual entities, nor the two categories of IRD vs. NIRD (calprotectin 155.7 vs. 96.99 ng/ml; NGAL 14 896 vs. 11 977 pg/ml; KIM-1 1388 vs. 1009 pg/ml; p > 0.05 each). Albumin exceeds the diagnostic power of the investigated biomarkers by far. CONCLUSIONS: The urinary biomarkers calprotectin, NGAL, and KIM-1 have no diagnostic value in the differentiation of primarily inflammatory vs. non-inflammatory etiologies of CKD.

Association of hyperuricemia and serum uric acid lowering therapy with mortality in hemodialysis patients.

INTRODUCTION: In the general population, hyperuricemia is associated with increased morbidity and mortality. Data on this association in hemodialysis patients is controversial. Moreover, it remains elusive whether serum uric acid (SUA) lowering therapy is associated with mortality. METHODS: Retrospective analysis of 601 patients on chronic hemodialysis therapy in five outpatient centers with a maximum follow-up of 100 and a mean follow-up of 41 months. Death was defined as primary endpoint. Cumulative survival was analyzed by Kaplan-Meier analysis and Cox regressions adjusted for age. FINDINGS: Cumulative survival rates were higher for those subjects with a higher than median SUA concentration both based on mean annual and baseline measurements (p < 0.05 each). There was no survival difference anymore after adjustment for age (p > 0.05 each). Stratification for SUA lowering therapy (allopurinol/febuxostat) had no impact on cumulative survival, neither in Kaplan Meier nor in Cox regression analyses (p > 0.05 each). Furthermore, Cox regression analysis excluded an increased cardiovascular mortality in subjects with hyperuricemia. DISCUSSION: In contrast to the general population, hyperuricemia is not associated with increased mortality in patients undergoing hemodialysis. Moreover, xanthine oxidase inhibition was not associated with a survival benefit in this analysis. These data do not support the use of SUA lowering medication in hemodialysis patients with asymptomatic hyperuricemia.

Prognostic Value of Urinary Calprotectin, NGAL and KIM-1 in Chronic Kidney Disease.

BACKGROUND/AIMS: Urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) do not only allow an early diagnosis of acute kidney injury, but also provide prognostic information in this setting. The present prospective study investigates, whether the urinary biomarkers NGAL, KIM-1 and calprotectin have prognostic information in chronic kidney disease (CKD) as well. METHODS: Urinary calprotectin, NGAL and KIM-1 concentrations were assessed in a study population of 143 patients with stable CKD comprising diabetic and hypertensive nephropathy, glomerulonephritis/vasculitis, and autosomal dominant polycystic kidney disease. An eGFR fluctuation > 5ml/min/1.73m2 in the past 12 months was defined as an exclusion criterion in order to exclude cases with acute on chronic kidney injury. Renal function was monitored for a median follow-up of 37 months. RESULTS: In the overall study population, all the three biomarkers failed to predict DeGFR and DACR from baseline to follow-up in linear regression analysis adjusted for age, gender, and baseline eGFR. Contrarily, baseline ACR was significantly associated with DeGFR (p< 0.001). In the subgroup of patients with vasculitis and glomerulonephritis, all the three biomarkers were significantly associated with DeGFR, with calprotectin having the highest regression coefficient. CONCLUSION: In contrast to the traditional biomarker "albuminuria", neither the inflammatory biomarker calprotectin, nor the tubular biomarkers NGAL and KIM-1, provide robust prognostic information on the loss or renal function in a heterogeneous CKD population. All of them, however, are candidate prognostic biomarkers in primarily inflammatory renal diseases.

Low-density lipoprotein apheresis is associated with removal of SARS-CoV-2 antibodies.

BACKGROUND: Low-density lipoprotein apheresis is not specific to lipoproteins but removes immunoglobulins as well. It remains elusive, whether protective SARS-CoV-2 antibodies after vaccination from COVID-19 are eliminated as well. METHODS: A cross-sectional case-control study on 55 patients undergoing weekly lipoprotein apheresis and 21 patients with comparable comorbidities and epidemiology not undergoing apheresis. SARS-CoV-2 IgG was assessed in all patients prior to apheresis and in 38 patients both before and after apheresis. RESULTS: SARS-CoV-2 IgG concentrations before a session of lipoprotein apheresis were comparable to control patients not undergoing apheresis(1727 IU/ml, IQR 365-2500) vs. 1652 IU/ml,(IQR408.8-2500), p = 0.78). SARS-CoV-2 IgG concentrations were reduced by lipoprotein apheresis from 1656 IU/ml(IQR 540.5-2500) prior to 1305 IU/ml (IQR 449-2500) afterwards(p < 0.0001). CONCLUSION: Lipoprotein apheresis removes SARS-CoV-2 IgG. The average elimination rate was 21.2%. In the present population of patients undergoing apheresis once weekly, however, the elimination did not lead to inferior concentrations compared to patients not undergoing lipoprotein apheresis.