Prognostic Value of C4d Immunolabelling in Adult Patients With IgA Vasculitis

Background and Objectives: Glomerular C4d deposits are associated the severity and outcomes of IgA nephropathy. Whether this holds true in immunoglobulin A vasculitis (IgAV) is not known. The main objective of the study was to analyze the prognostic value of glomerular C4d immunolabelling on kidney impairment in adults with IgAV.Design, Setting, Participants, Measurements: This retrospective cohort study included 120 adults with IgAV and a kidney biopsy performed between 1995 and 2018 in two French university hospital centers. All paraffin-embedded biopsies were reassessed according to Oxford classification. Immunofluorescence for C4d was performed in all cases. For analysis, patients were grouped according to positivity for C4d in the glomerular area. The main outcome was a composite endpoint of 50% increase in 24 h-proteinuria, or eGFR decrease by 50%, or kidney replacement therapy.Results: The median follow-up was 28.3 months. Twenty-three patients met the composite endpoint, 12 for kidney replacement therapy, 6 for an eGFR decrease >50% and 5 for a >50% increase in proteinuria. At time of biopsy, the median proteinuria was 1.9 g/24 h and the median eGFR 73.5 mL/min/1.73 m2. Among the 102 patients evaluable for C4d, 24 were positive on >30% glomeruli, mainly with a parieto-mesangial pattern. In this group, the initial proteinuria was more frequently nephrotic than in the C4d– group (60% vs. 33%, P = 0.039). Mesangial hypercellularity was more frequent in the C4d+ group (42% vs. 13%; P = 0.006) whereas macroscopic hematuria was more frequent in the C4d– group (18% vs. 0%; P = 0.03). After a median follow-up of 28 months, kidney survival did not differ according to C4d status.Conclusion: In a population of adult IgAV patients, glomerular positivity for C4d was associated with the severity of the kidney disease at presentation, but not with subsequent renal function deterioration.

Urinary L-Type Fatty Acid-Binding Protein is a Predictor of Cisplatin-Induced Acute Kidney Injury.

Background Although cisplatin-based chemotherapy is a standard treatment for urothelial carcinoma, it often causes acute kidney injury (AKI). AKI and dysfunction are observed in 25–35% of cisplatin-based chemotherapy patients, who may require treatment down-titration or withdrawal. In this study, we evaluated whether urinary L-FABP is a marker for early diagnosis of cisplatin-caused AKI. Methods We included 42 adult patients who underwent cisplatin-based chemotherapy for bladder cancer or upper tract urothelial carcinoma from January 2018 to March 2019. Urinary L-FABP and serum creatinine were measured at 2 and 6 hours, and 1, 2, 3, 7 and 28 days after taking cisplatin. Results In the first week after receiving cisplatin, 10 patients (23.8%) were diagnosed with AKI (AKI+ group). Pre-treatment (baseline) measurements did not significantly differ between the AKI+ and AKI− groups. However, urinary L-FABP concentrations rapidly increased in the AKI+ group and were significantly greater than in the AKI− group at Hour 2, Hour 6, Day 1 and Day 2. Serum creatinine also significantly differed between the AKI+ group and the AKI− group on Days 3 and 7. Conclusions Acute renal function deterioration was predicted by increased urinary L-FABP excretion within six hours after receiving CIS-CT and, in those with AKI, the increase in urinary L-FABP excretion preceded the rise in sCr by over 2 days. In contrast, no appreciable changes in urinary L-FABP levels were observed in patients with stable renal function throughout the whole observation period. So early increase in urinary L-FABP may identify patients at risk of cisplatin-induced AKI, who might benefit from treatment to prevent nephrotoxicity. Trial registration: This study was retrospectively registered.

Renal function deterioration is an independent mortality determinant in Koreans diagnosed with lupus nephritis

Objective To evaluate the predictors of mortality, mortality rate, and causes of death in patients with lupus nephritis (LN) depending on final renal function. Methods The cohort included 401 Korean patients diagnosed with LN between 1985 and 2019. We retrospectively analyzed the clinical and laboratory indices, treatment response, and the final renal function. The final renal function was defined by the last stable level of eGFR measured in an out-patient department more than 3 times before death occurred and was categorized into five groups depending on CKD stage. Results The median follow-up time after the diagnosis of LN was 131 months. No difference in baseline demographic characteristics and laboratory findings was found except for the proportion of Hb less than 10 mg/dl and baseline eGFR ( p = 0.011 and 0.037). We found no significant differences in therapeutic parameters, but all the response parameters including treatment response at 6 months ( p = 0.004) and 12 months ( p = 0.004), time to remission ( p < 0.001), final renal response ( p < 0.001), and the final renal function ( p < 0.001) differed significantly between the two groups. In multivariate Cox proportional hazards analysis, the final renal function was an independent risk factor predicting mortality. The main causes of death were infection and SLE flare. Contrary to existing knowledge, SLE flare also triggered mortality in a few patients with LN progressed to end-stage renal disease (ESRD). Only two cases of mortality occurred in the kidney transplantation (KT) group ( n = 25) with a median follow-up period of 224 months. The overall mortality rates calculated using the Kaplan–Meier method were 6.8%, 10.3%, 19.7%, and 28.0% at 5, 10, 20, and 30 years, respectively. Conclusion Renal function deterioration was an independent determinant of mortality in Korean patients with LN. SLE flare also caused mortality in patients with LN who required maintenance dialysis, suggesting the benefit of KT on lupus activity and survival.

Neutrophil gelatinase-associated lipocalin partly reflects the dynamic changes of renal function among chronic hepatitis C patients receiving direct-acting antivirals

Background Changes in renal function in chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs) are controversial. The evolution of neutrophil gelatinase-associated lipocalin (NGAL) in these patients remains unclear. Methods A total of 232 CHC patients receiving DAA at Dalin Tzu Chi Hospital from May 2016 to February 2019, were enrolled in this retrospective study. Grade 2/3 renal function deterioration, defined as a decrease in eGFR between 10% and 50% from baseline (BL) to 12 weeks after the end of treatment (P12), was investigated for its association with BL characteristics. The changes in renal function and NGAL levels were also analyzed at the SOF-base or nonSOF-base DAA. Results Sixty-two patients (26.7%) had grade 2/3 renal function deterioration at P12 after DAA therapy. Univariate analysis showed that it was associated with age (P = 0.038). Multivariate analysis indicated that age (OR = 1.033, 95% CI: 1.004–1.064, P = 0.027), sex (male; OR = 2.039, 95% CI: 1.093–3.804, P = 0.025), ACEI/ARB use (OR = 2.493, 95% CI: 1.016–6.119, P = 0.046), and BL NGAL (OR = 1.033, 95% CI: 1.001–1.067, P = 0.046) positively correlated with grade 2/3 renal function deterioration. Furthermore, eGFR was decreased (P = 0.009) and NGAL was increased (P = 0.004) from BL to P12 in CHC patients receiving SOF-based DAA. Conclusions Of the CHC patients receiving DAA therapy, 26.7% had grade 2/3 renal function deterioration at P12, and it was associated with older age, gender being male, ACEI/ARB use, and higher BL NGAL levels. In addition, NGAL might be a biomarker of nephrotoxicity at P12 in patients receiving SOF-based DAA.

Histopathological nephrotoxic features of high oral doses of ubiquinone in rats

Co-enzyme Q10 (Co-Q10) plays a key role in the cellular respiration for the production of ATP. The toxicity of quinones to the kidney appears to depend on variety of factors, including genetic polymorphisms and the individual’s comorbidites. The aim of the present study was to assess histologically the nephrotoxic effects of 6 weeks daily oral intake of Co-Q10 in experimental animals. Twenty-five Wistar rats weighing between 220-270 g were randomly divided into two groups: experimental “treated” and control “untreated” groups (n=15, n=10, respectively). The animals of the experimental group received 300 mg/kg daily dose of gelatinous capsules of Co-Q10 by oral gavage for six weeks. At the end of the study, all animals were sacrificed under general anesthesia and samples of the kidneys were excised for microscopic histopathological assessment of renal tissue using stain. The experimental group showed a range of mild to severe dilatation of Bowman’s space, with a mean corpuscular diameter of 294±38 µm that was significantly higher (p <0.05) than that of the untreated control group 208±31 µm. Shrinkage to complete destruction of the glomeruli was observed in the experimental group only. The long-term use of high doses of Co-Q10 had revealed a selective nephrotoxicity towards podocytes. This might be a risk factor leading to renal proximal tubular necrosis in rats and the subsequent renal function deterioration.