Intensive haemodialysis using PMMA dialyser does not increase renal response rate in multiple myeloma patients with acute kidney injury.

BACKGROUND: Intensive haemodialysis (IHD) in addition to bortezomib-based chemotherapy might be efficient to rapidly decrease serum immunoglobulin-free light chains removal in patients with multiple myeloma (MM) and to improve renal prognosis and survival. METHODS: The aim of this retrospective multi-centre study was to compare the efficacy (renal recovery rate) of IHD and of standard haemodialysis (SHD) in patients with MM and dialysis-dependent acute kidney injury (AKI), concomitantly treated with bortezomib-based chemotherapy. RESULTS: We selected 41 patients with MM and dialysis-dependent AKI, most likely due to myeloma cast nephropathy (MCN), and who were treated in eight French hospitals between January 2007 and June 2011. Patients were classified in two groups according to dialysis regimen: IHD [n = 21, with a mean of 11.3 dialysis sessions all with poly(methyl methacrylate) (PMMA) membranes for 13.2 days] and SHD (n = 20 patients, mostly three times per week, 31% with PMMA membrane). The main outcome was dialysis-independence at 3 months. At 3 months, 15 patients could stop dialysis: 8 (38.1%) in the IHD and 7 (35%) in the SHD group (P = 1). Moreover, 14 (56%) of the 25 patients who did show haematological response and only one of the 16 patients who did not were dialysis-independent (P = 0.002) at 3 months. CONCLUSIONS: The results of this retrospective study did not show any clear renal benefit of IHD in patients with MM and MCN compared with SHD. Conversely, they underline the importance of the haematological response to chemotherapy for the renal response and patient prognosis.

[Is cancer incidence different between type 2 diabetes patients compared to non-diabetics in hemodialysis? A study from the REIN registry]. / Patients en hémodialyse : l'incidence de cancer est-elle différente entre les diabétiques de type 2 comparés aux non-diabétiques ? Une étude du registre REIN.

BACKGROUND AND OBJECTIVES: In France, diabetes mellitus is now the second cause of end stage renal disease. In a large previous French national study, we observed that dialyzed diabetics have a significant lower risk of death by cancer. This first study was focused on cancer death but did not investigate cancer incidence. In this context, the aim of this second study was to compare the incidence of cancer in diabetic dialyzed patients compared to non-diabetic dialyzed patients in a French region. METHODS: This epidemiologic multicentric study included 588 diabetic and non-diabetic patients starting hemodialysis between 2002 and 2007 in Bretagne. Data were issued from REIN registry and cancer incidence were individually collected from medical records. Diabetics and non-diabetics were matched one by one on age, sex and year of dialysis initiation. RESULTS: During the follow-up, we observed 28 cancers (9.4%) in diabetic patients and 26 cancers (8.9%) in non-diabetics patients. The cumulative incidence to develop a cancer 2 years after the dialysis start was approximately 6% in both diabetics and non-diabetics patients. In univariate Fine and Gray analysis, BMI, hemoglobin, statin use had P-value<0.2. However, in the adjusted model, these variables were not significantly associated with cancer incidence. CONCLUSION: This study lead on a little number of dialyzed patients did not show any significant difference on cancer incidence between diabetic and non-diabetic patients after hemodialysis start.

Warfarin-related nephropathy induced by three different vitamin K antagonists: analysis of 13 biopsy-proven cases.

Background: Acute kidney injury (AKI) with renal tubular obstruction by red blood cell casts (RBCC) has been described in patients treated with warfarin and is known as warfarin-related nephropathy (WRN). Methods: To determine whether other vitamin K antagonists (VKA) cause WRN, we retrospectively collected and analyzed the clinical and histological data of 13 patients treated with different VKA (seven with fluindione, four with warfarin and two with acenocoumarol) in seven French hospitals. Results: They all developed gross hematuria following overanticoagulation complicated by severe AKI (median serum creatinine concentration = 693 µmol/L). Histological analysis of the kidney biopsies highlighted the presence of intratubular RBCC and acute tubular necrosis in all patients and of an underlying kidney disease in 12 patients. WRN was suspected in patients treated with warfarin; however, the initial diagnosis was incorrect in six of the nine patients treated with other VKA. Nine patients progressed to chronic kidney disease, one fully recovered renal function, two died and one still needs dialysis. Conclusions: This is the first report of AKI caused by fluindione. In agreement with the recent publication on AKI in two patients treated with dabigatran, we suggest that the term 'anticoagulant-related nephropathy' is more appropriate than WRN. Gross hematuria in patients with an underlying kidney disease and treated with VKA requires rapid control of the international normalized ratio and renal function monitoring.

PKD2-Related Autosomal Dominant Polycystic Kidney Disease: Prevalence, Clinical Presentation, Mutation Spectrum, and Prognosis.

BACKGROUND: PKD2-related autosomal dominant polycystic kidney disease (ADPKD) is widely acknowledged to be of milder severity than PKD1-related disease, but population-based studies depicting the exact burden of the disease are lacking. We aimed to revisit PKD2 prevalence, clinical presentation, mutation spectrum, and prognosis through the Genkyst cohort. STUDY DESIGN: Case series, January 2010 to March 2016. SETTINGS & PARTICIPANTS: Genkyst study participants are individuals older than 18 years from 22 nephrology centers from western France with a diagnosis of ADPKD based on Pei criteria or at least 10 bilateral kidney cysts in the absence of a familial history. Publicly available whole-exome sequencing data from the ExAC database were used to provide an estimate of the genetic prevalence of the disease. OUTCOMES: Molecular analysis of PKD1 and PKD2 genes. Renal survival, age- and sex-adjusted estimated glomerular filtration rate. RESULTS: The Genkyst cohort included 293 patients with PKD2 mutations (203 pedigrees). PKD2 patients with a nephrology follow-up corresponded to 0.63 (95% CI, 0.54-0.72)/10,000 in Brittany, while PKD2 genetic prevalence was calculated at 1.64 (95% CI, 1.10-3.51)/10,000 inhabitants in the European population. Median age at diagnosis was 42 years. Flank pain was reported in 38.9%; macroscopic hematuria, in 31.1%; and cyst infections, in 15.3% of patients. At age 60 years, the cumulative probability of end-stage renal disease (ESRD) was 9.8% (95% CI, 5.2%-14.4%), whereas the probability of hypertension was 75.2% (95% CI, 68.5%-81.9%). Although there was no sex influence on renal survival, men had lower kidney function than women. Nontruncating mutations (n=36) were associated with higher age-adjusted estimated glomerular filtration rates. Among the 18 patients with more severe outcomes (ESRD before age 60), 44% had associated conditions or nephropathies likely to account for the early progression to ESRD. LIMITATIONS: Younger patients and patients presenting with milder forms of PKD2-related disease may not be diagnosed or referred to nephrology centers. CONCLUSIONS: Patients with PKD2-related ADPKD typically present with mild disease. In case of accelerated degradation of kidney function, a concomitant nephropathy should be ruled out.

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease.

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.

[Focusing on peritoneal dialysis adequacy]. / Adéquation en dialyse péritonéale : mise au point.

The optimal method to assess the adequacy of peritoneal dialysis therapies is controversial. Today, the adequacy must not be considered as a number or a concept assessed only by two parameters (total KT/V urea and total solute clearance) but defined by many more items. In the absence of data, based on theoretical considerations, the reanalysis of the CANUSA study showed that renal kidney function, rather than peritoneal clearance, was associated with improved survival. Residual renal function is considered as a major predictor factor of cardiovascular mortality. Results of this reanalysis were supported by the adequacy data in ADEMEX, EAPOS and ANZDATA studies. Therefore, clinical assessment plays a major role in PD adequacy. The management of fluid balance, the regular monitoring of malnutrition, the control of mineral metabolism and particularly the glucose load, considered as the "corner-stone" of the system, are the main points to be considered in the adequacy of PD patients. The essential goal is to minimize glucose load by glucose-sparing strategies in order to reduce the neoangiogenesis of the peritoneal membrane.

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.