Long-term effects of citric acid-based bicarbonate haemodialysis on patient outcomes: a survival propensity score-matched study in western France.

BACKGROUND: Citric acid-based bicarbonate haemodialysis (CIT-HD) has gained more clinical acceptance over the last few years in France and is a substitute for other acidifiers [e.g. acetic acid (CH3COOH) and hydrochloric acid (HCl)]. This trend was justified by several clinical benefits compared with CH3COOH as well as the desire to avoid the consequences of the corrosive action of HCl, but a nationwide clinical report raised concerns about the long-term safety of CIT-HD. The aim of this study was to assess the long-term effects of CIT-HD exposure on patient outcomes in western France. METHODS: This is a population-based retrospective multicentre observational study performed in 1132 incident end-stage kidney disease patients in five sanitary territories in western France who started their renal replacement therapy after 1 January 2008 and followed up through 15 October 2018. Relevant data, collected prospectively with the same medical software, were anonymously aggregated for the purposes of the study. The primary goal of this study was to investigate the effects of citrate exposure on all-cause mortality. To provide a control group to CIT-HD one, propensity score matching (PSM) at 2:1 was performed in two steps: the first analysis was intended to be exploratory, comparing patients who received citrate ≤80% of the time (CIT-HD ≤80) versus those who received citrate >80% of the time (CIT-HD >80), while the second analysis was intended to be explanatory in comparing patients with 0% (CIT-HD0) versus 100% citrate time exposure (CIT-HD100). RESULTS: After PSM, in the exploratory part of the analysis, 432 CIT-HD ≤80 patients were compared with 216 CIT-HD >80 patients and no difference was found for all-cause mortality using the Kaplan-Meier model (log-rank 0.97), univariate Cox regression analysis {hazard ratio [HR] 1.01 [95% confidence interval (CI) 0.71-1.40]} and multivariate Cox regression analysis [HR 1.11 (95% CI 0.76-1.61)] when adjusted for nine variables with clinical pertinence and high statistical relevance in the univariate analysis. In the explanatory part of the analysis, 316 CIT-HD0 patients were then compared with 158 CIT-HD100 patients and no difference was found using the Kaplan-Meier model (log-rank 0.06), univariate Cox regression analysis [HR 0.69 (95% CI 0.47-1.03)] and multivariate Cox regression analysis [HR 0.87 (95% CI 0.57-1.33)] when adjusted for seven variables with clinical pertinence and high statistical relevance in the univariate analysis. CONCLUSIONS: Findings of this study support the notion that CIT-HD exposure ≤6 years has no significant effect on all-cause mortality in HD patients. This finding remains true for patients receiving high-volume online haemodiafiltration, a modality most frequently prescribed in this cohort.

[Disseminated tuberculosis revealed by obstructive and prerenal acute kidney failure]. / Tuberculose disséminée révélée par une insuffisance rénale aiguë obstructive et fonctionnelle.

A 56-year-old Philippine seaman without any medical history presented an obstructive and prerenal acute kidney failure near the coasts of Normandy. He was hospitalized in intensive care units because of the seriousness of kidney failure and because of impaired consciousness. Abdominal computed tomography showed a destroyed left kidney, a right hydronephrosis and ureteral strictures, which is typical of urinary tuberculosis. Koch bacillus was positive in urine sample, confirming the diagnosis. Thoracic computed tomography, brain magnetic resonance imaging revealed a tuberculosis miliary with concomitant tuberculous meningitis and intracranial tuberculoma. Intravenous hydration and a double J ureteral catheter improved renal function. Stage 4 chronic kidney disease persisted. A four antituberculous therapy associated with corticotherapy for the meningitis was initiated. We discuss of urinary tuberculosis based on literature data about epidemiology, physiopathology, diagnosis and treatment.

Are all dialyzers compatible with the convective volumes suggested for postdilution online hemodiafiltration?

INTRODUCTION: The recent analysis of 4 randomized controlled trials has confirmed the lower mortality risk for postdilution online hemodiafiltration (OL-HDF) compared to hemodialysis, and above all for patients with the highest delivered body surface area standardized convective volume (CV/BSA >23 L/1.73 m²/session). Since the impact of the dialyzers used in these trials has never been studied, we retrospectively analyzed clinical tests carried out with 19 commonly used dialyzers. The aim was to provide information on their performances and behavior to aid in an objective choice for therapies associated with OL-HDF. METHODS: "Efficiency" was evaluated by measuring the reduction ratio of beta-2 microglobulin (RRß2M) and myoglobin (RRmyo) for a CV/BSA between 0 and 30 L, extrapolating them at CV/BSA = 23 L. "Safety" was defined by the safe CV (CVsafe), corresponding to the CV/BSA above which albumin loss is >5 g/session. RESULTS: With CV/BSA = 23 L, all the dialyzers ensure an optimal ß2M extraction (RRß2M: 76%-84.5%). For myoglobin, efficiency disparities are bigger (RRmyo: 40%-85%). Above all, 4/19 dialyzers lose more than 5 g albumin and should not be used under these conditions. CONCLUSIONS: It is recommended to prescribe dialyzers that are above all safe. Moreover, if one considers that the removal of middle molecule solutes prevails over the CV necessary for their transmembrane transport, some dialyzers that are more efficient with CV/BSA <23 L than others with CV/BSA >= 23 L might then be prescribed when the conditions do not permit the suggested CV/BSA goal to be achieved.

Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

OBJECTIVE: To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). METHODS: We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. RESULTS: Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. CONCLUSION: This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

Acute and chronic nephropathy induced by fluindione must be addressed.

BACKGROUND: Among the vitamin K antagonists (VKA), indanedione-derived VKA is suspected to induce an immunoallergic risk. One indanedione-derived VKA, fluindione, is still being used in France. The aim of this study was to evaluate the contribution of VKA to acute and chronic nephritis. METHODS: Twenty-four cases of biopsy proven acute interstitial nephritis (AIN) were retrospectively selected, based on a first intake of VKA within the previous 12 months as well as an increase of at least 50% of the basal level of serum creatinine. The 24 cases were all treated with fluindione VKA and not with coumarinic VKA. RESULTS: The subjects studied included 20 men and 4 women, with a mean age of 73.0±9.3 years (range: 44-84). The delay between fluindione introduction and the appearance of an AIN, proven by biopsy when available, was 11.9±6.9 weeks (range: 3-28). Creatinine increased from 123.0±56.4 µmol/L (range: 56-335) at fluindione introduction to 460.7±265.3 µmol/L (range: 109-1200) at the time of AIN discovery. The treatment then consisted of stopping the fluindione and introducing steroids for 21 patients. If a VKA was necessary, fluindione was replaced by a coumarinic VKA. After 6 months, 1 patient died and 15 patients presented severe chronic kidney disease (CKD Stages 4-5). Two patients still required chronic dialysis after 6 months and five patients after 3 years. Patients with pre-existing kidney disease were more prone to develop severe CKD with fluindione. CONCLUSION: In this large study, arguments are presented to incriminate fluindione in the induction of acute and chronic nephritis.

Factors affecting outcome and prognosis in membranous lupus nephropathy.

BACKGROUND: This study was designed to review the prognosis and the predictors of renal outcome in patients with membranous lupus nephropathy (MLN) with no or mild mesangial proliferation. METHODS: The medical records of patients (n=66) with biopsy-proven MLN, WHO class VA, and class VB without any past history of proliferative lupus nephropathy (PLN) were reviewed retrospectively. RESULTS: The mean follow-up was 6.9+/-0.2 years and renal survival at 5 and 10 years was 97+/-2 and 88+/-6%. Twenty-nine patients underwent a second renal biopsy during follow-up. Fourteen of these patients (21%) had lesions of PLN. Among them, four reached end-stage renal disease (ESRD) despite immunosuppressive treatment. The probability of a transition from MLN to PLN at 10 years was 35+/-8%. Two other patients reached ESRD but did not have repeat renal biopsies and two had biopsy-proven progression to fibrosis. Independent risk factors associated with the doubling of creatinine were transition into PLN and the occurrence of a thrombosis during follow-up. The only predictor of ESRD was the haemoglobin level. PLN was not a predictor of ESRD but the efficient treatment of this form of lupus nephritis prevented that outcome. CONCLUSIONS: With a long follow-up, our study noted a high frequency of transition into PLN in a large cohort of patients with MLN. Steroid usage was not predictive of outcome and did not affect renal survival, a result that must be qualified in light of the highly variable duration of treatments with steroids. The early screening and treatment of PLN is the main benefit of the close follow-up of patients with MLN. Progression to ESRD with only fibrosis remains a rare event.

Survival of elderly patients on peritoneal dialysis: retrospective study of 292 patients, from 1982 to 1999.

BACKGROUND: Dialysis is becoming increasingly frequent in patients over 75 years of age. Age is a superimposed comorbid factor commonly associated with poor prognosis in these patients. OBJECTIVE: To analyze the survival of 292 patients aged over 75 years on initiation of peritoneal dialysis (PD) from September 1982 to September 1999. DESIGN: Retrospective study. SETTING: Nephrology department in a University Hospital. RESULTS: Mean age was 81.5 years (range 75-92 years); 178 patients were over 80 years and 60 patients were over 85 years. Sex ratio was 136F/156M. Ninety-day mortality rate was 12%. Excluding the first 3 months, median patient survival was 21.6 months; 226 patients died on PD and 24 were shifted to hemodialysis. Survival was inversely correlated with the Charlson combined comorbidity index (CCI), but independent of predialysis hemoglobin and serum albumin levels. Over three selected periods, 1982-1989, 1989-1995, and 1995-1999, an increase was found in mean age (79.7 +/- 3.3, 82.6 +/- 3.9, and 81.8 +/- 4.4 years; p < 0.001), CCI (7.6 +/- 1.59, 8.0 +/- 1.52, and 8.5 +/- 1.63; p = 0.01), and predialysis creatinine clearance (6.2 +/- 2.3, 6.4 +/- 2.4, and 9.8 +/- 3.8 mL/minute; p < 0.001). Median survival was similar in the various selected periods (21.0, 21.5, and 25.4 months). The incidence of peritonitis decreased from 0.63 to 0.21 episodes per patient year. CONCLUSION: From 1982 to 1999, mean age and comorbidity increased on initiation of dialysis in elderly patients, with no increase in mortality. Survival in elderly patients on PD was related to the age-comorbidity index.

Vimentin affects localization and activity of sodium-glucose cotransporter SGLT1 in membrane rafts.

It has been reported that vimentin, a cytoskeleton filament that is expressed only in mesenchymal cells after birth, is re-expressed in epithelial cells in vivo under pathological conditions and in vitro in primary culture. Whether vimentin re-expression is only a marker of cellular dedifferentiation or is instrumental in the maintenance of cell structure and/or function is a matter of debate. To address this issue, we used renal proximal tubular cells in primary culture from vimentin-null mice (Vim(-/-)) and from wild-type littermates (Vim(+/+)). The absence of vimentin did not affect cell morphology, proliferation and activity of hydrolases, but dramatically decreased Na-glucose cotransport activity. This phenotype was associated with a specific reduction of SGLT1 protein in the detergent-resistant membrane microdomains (DRM). In Vim(+/+) cells, disruption of these microdomains by methyl-beta-cyclodextrin decreased SGLT1 protein abundance in DRM, a change that was paralleled by a decrease of Na-glucose transport activity. Importantly, we showed that vimentin is located to DRM, but it disappeared after methyl-beta-cyclodextrin treatment. In Vim(-/-) cells, supplementation of cholesterol with cholesterol-methyl-beta-cyclodextrin complexes completely restored Na-glucose transport activity. Interestingly, neither cholesterol content nor cholesterol metabolism changed in Vim(-/-) cells. Our results are consistent with the view that re-expression of vimentin in epithelial cells could be instrumental to maintain the physical state of rafts and, thus, the function of DRM-associated proteins.