Olivier Moranne

Timing of Onset of CKD-Related Metabolic Complications

Chronic kidney disease (CKD) guidelines recommend evaluating patients with GFR <60 ml/min per 1.73 m(2) for complications, but little evidence supports the use of a single GFR threshold for all metabolic disorders. We used data from the NephroTest cohort, including 1038 adult patients who had stages 2 through 5 CKD and were not on dialysis, to study the occurrence of metabolic complications. GFR was measured using renal clearance of (51)Cr-EDTA (mGFR) and estimated using two equations derived from the Modification of Diet in Renal Disease study. As mGFR decreased from 60 to 90 to <20 ml/min per 1.73 m(2), the prevalence of hyperparathyroidism increased from 17 to 85%, anemia from 8 to 41%, hyperphosphatemia from 1 to 30%, metabolic acidosis from 2 to 39%, and hyperkalemia from 2 to 42%. Factors most strongly associated with metabolic complications, independent of mGFR, were younger age for acidosis and hyperphosphatemia, presence of diabetes for acidosis, diabetic kidney disease for anemia, and both male gender and the use of inhibitors of the renin-angiotensin system for hyperkalemia. mGFR thresholds for detecting complications with 90% sensitivity were 50, 44, 40, 39, and 37 ml/min per 1.73 m(2) for hyperparathyroidism, anemia, acidosis, hyperkalemia, and hyperphosphatemia, respectively. Analysis using estimated GFR produced similar results. In summary, this study describes the onset of CKD-related complications at different levels of GFR; anemia and hyperparathyroidism occur earlier than acidosis, hyperkalemia, and hyperphosphatemia.

A clinical score to predict 6-month prognosis in elderly patients starting dialysis for end-stage renal disease.

AIMnThe aim of this study was to develop and validate a prognostic score for 6-month mortality in elderly patients starting dialysis for end-stage renal disease.nnnMETHODSnUsing data from the French Rein registry, we developed a prognostic score in a training sample of 2500 patients aged 75 years or older who started dialysis between 2002 and 2006, which we validated in a similar sample of 1642 patients. Multivariate logistic regression with 500 bootstrap samples allowed us to select risk factors from 19 demographic and baseline clinical variables.nnnRESULTSnThe overall 6-month mortality was 19%. Age was not associated with early mortality. Nine risk factors were selected and points assigned for the score were as follows: body mass index <18.5 kg/m2 (2 points), diabetes (1), congestive heart failure stages III to IV (2), peripheral vascular disease stages III to IV (2), dysrhythmia (1), active malignancy (1), severe behavioural disorder (2), total dependency for transfers (3) and unplanned dialysis (2). The median score was 2. Mortality rates ranged from 8% in the lowest risk group (0 point) to 70% in the highest risk group (> or =9 points) and 17% in the median group (2 points). Seventeen percent of all deaths occurred after withdrawal from dialysis, ranging from 0% for a score of 0-1 to 15% for a score of 7 or higher.nnnCONCLUSIONSnThis simple clinical score effectively predicts short-term prognosis among elderly patients starting dialysis. It should help to illuminate clinical decision making, but cannot be used to withhold dialysis. It ought to only be used by nephrologists to facilitate the discussion with the patients and their families.

Pitfalls of Measuring Total Blood Calcium in Patients with CKD

Disorders of mineral and bone metabolism are prevalent in patients with chronic kidney disease (CKD). The recent National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend that blood calcium (Ca) be regularly measured in patients with stages 3 to 5 CKD. The Kidney Disease: Improving Global Outcomes (KDIGO) position states that the measurement of ionized Ca (iCa) is preferred and that if total Ca (tCa) concentration is used instead, then it should be adjusted in the setting of hypoalbuminemia. In 691 consecutive patients with stages 3 to 5 CKD, we compared the ability of noncorrected and albumin-corrected tCa concentration to identify low, normal, or high iCa concentration. The agreement between noncorrected or albumin-corrected tCa and iCa was only fair. The risk for underestimating ionized calcium was independently increased by a low total CO(2) concentration when either noncorrected or albumin-corrected Ca was used and by a low albumin concentration only when noncorrected tCa was used. The risk for overestimating iCa was increased by a low albumin concentration only when albumin-corrected Ca was used. In conclusion, albumin-corrected tCa does not predict iCa better than noncorrected tCa. Moreover, both noncorrected and albumin-corrected tCa concentrations poorly predict hypo- or hypercalcemia in patients with CKD.

MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients.

Background The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed. Methods We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of 51Cr-EDTA (n=337). Results Mean measured GFR (mGFR) was 50±19 mL/min/1.73 m2. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR <60 mL/min/1.73 m2 and between 60 and 90 mL/min/1.73 m2. For mGFR >90 mL/min/1.73 m2, there were no significant differences between the two equations in terms of performance. Conclusions The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages.

GFR Estimation Using Standardized Cystatin C in Kidney Transplant Recipients

BACKGROUNDnThe utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients.nnnSTUDY DESIGNnStudy of diagnostic test accuracy.nnnSETTING & PARTICIPANTSn670 kidney transplant recipients from 3 centers undergoing glomerular filtration rate (GFR) measurements from December 2006 to November 2012.nnnINDEX TESTnEstimated GFR (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysC-based CKD-EPI equations (eGFR(cys) and eGFR(cr-cys), respectively) and the 2009 SCr-based CKD-EPI equation (eGFR(cr)), with SCysC and SCr measured at a single laboratory between April 2011 and June 2011.nnnREFERENCE TESTnMeasured GFR (mGFR) using urinary clearance of inulin.nnnRESULTSnBias (the difference between mGFR and eGFR) was significantly smaller for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (-2.82 and -0.54 vs +4.4 mL/min/1.73 m(2), respectively; P < 0.001). Precision (standard deviation of the mean bias) also was better for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (12 and 11 vs 13 mL/min/1.73 m(2) [P < 0.001 for both comparisons]). Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for eGFR(cys) and eGFR(cr-cys) versus eGFR(cr) (81% and 86% vs 75%, respectively [P = 0.004 and P < 0.001]). Net reclassification index with respect to mGFR of 30 mL/min/1.73 m(2) for eGFR(cr-cys) and eGFR(cys) versus eGFR(cr) was 18.8% [95% CI, 8.6%-28.9%] and 22.5% [95% CI, 10.2%-34.9%].nnnLIMITATIONSnPatients were exclusively of European descent; association with transplant outcome was not evaluated.nnnCONCLUSIONSnOur data validate the use of both the newly developed SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant recipients. Both equations perform better than the SCr-based CKD-EPI equation (2009).

Creatinine-or cystatin C-based equations to estimate glomerular filtration in the general population: impact on the epidemiology of chronic kidney disease

BackgroundChronic kidney disease (CKD) is a major issue in public health. Its prevalence has been calculated using estimation of glomerular filtration rate (GFR) by the creatinine-based equations developed in the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study. Recently, new equations based either on cystatin C (CKD-EPI Cys) or both cystatin and creatinine (CKD-EPI mix) have been proposed by the CKD-EPI consortium. The aim of this study was to measure the difference in the prevalence of stage 3 CKD, defined as an estimated GFR less than 60xa0mL/min/1.73xa0m2, in a population using these four equations.MethodsCKD screening was performed in the Province of Liège, Belgium. On a voluntary basis, people aged over 50xa0years have been screened. GFR was estimated by the four equations. Stage 3 CKD was defined as a GFR less than 60xa0mL/min/1.73xa0m2.ResultsThe population screened consisted of 4189 people (47% were men, mean age 63u2009±u20097y). Their mean serum creatinine and plasma cystatin C levels were 0.88u2009±u20090.21xa0mg/dL and 0.85u2009±u20090.17xa0mg/L, respectively. The prevalence of CKD in this population using the MDRD, the CKD-EPI, the CKD-EPI Cys and the CKD-EPI mix equations was 13%, 9.8%, 4.7% and 5%, respectively. The prevalence of CKD was significantly higher with the creatinine-based (MDRD and the CKD-EPI) equations compared to the new cystatin C-based equations.ConclusionsPrevalence of CKD varies strongly depending on the method used to estimate GFR. Such discrepancies are of importance and must be confirmed and explained by additional studies, notably by studies using GFR measured with a reference method.Trial registrationB70720071509

Characteristics and Treatment Course of Patients Older Than 75 Years, Reaching End-Stage Renal Failure in France. The PSPA Study

BACKGROUNDnThe age of patients with end-stage renal disease is increasing in Europe and United States. In France, patients older than 75 years represent 40% of the patients who start renal replacement therapy (dialysis or renal transplantation). In these elderly patients with many comorbidities, the benefit of dialysis remains controversial. To provide clear information to patients about diagnosis, prognosis, and all treatment options, more data are needed on their clinical characteristics, therapeutic projects, and outcome.nnnMETHODSnResearchers present here the ongoing Parcours de Soins des PersonnesAgées (PSPA) multicenter prospective study, which includes 581 patients with a mean age of 82±5 years and an estimated glomerular filtration rate (by sMDRD) of 14±4ml/min/1.73m(2) without dialysis.nnnRESULTSnDespite a high prevalence of associated comorbidities, most of the patients are autonomous, living at home. Less than 10% are followed jointly by a nephrologist and a geriatrician. At inclusion, postponed dialysis decision due to stable estimated glomerular filtration rate was reported in 43%, 17% of the patients are under evaluation, the decision to start dialysis was chosen in 24% of the patients, nondialysis decision was decided in 16%.nnnCONCLUSIONSnGeriatricians expertise may help nephrologists to identify patients at high risk of early death for who nondialysis care may be discussed. They also may be more able to evaluate and anticipate the impact of such restricting treatments. A multidisciplinary approach of these old and frail patients needs to be reinforced.

Determinants and Changes Associated with Aldosterone Breakthrough after Angiotensin II Receptor Blockade in Patients with Type 2 Diabetes with Overt Nephropathy

BACKGROUND AND OBJECTIVESnInhibition of the renin-angiotensin-aldosterone system decreases proteinuria and slows estimated GFR decline in patients with type 2 diabetes mellitus with overt nephropathy. Serum aldosterone levels may increase during renin-angiotensin-aldosterone system blockade. The determinants and consequences of this aldosterone breakthrough remain unknown.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnThis study examined the incidence, determinants, and changes associated with aldosterone breakthrough in a posthoc analysis of a randomized study that compared the effect of two angiotensin II receptor blockers in patients with type 2 diabetes mellitus with overt nephropathy.nnnRESULTSnOf 567 of 860 participants included in this posthoc analysis, 28% of participants developed aldosterone breakthrough, which was defined by an increase greater than 10% over baseline values of serum aldosterone levels after 1 year of angiotensin II receptor blocker treatment. Factors independently associated with aldosterone breakthrough at 1 year were lower serum aldosterone and potassium levels at baseline, higher decreases in sodium intake, systolic BP, and estimated GFR from baseline to 1 year, and use of losartan versus telmisartan. Aldosterone breakthrough at 6 months was not sustained at 1 year in 69% of cases, and it did not predict estimated GFR decrease and proteinuria increase between 6 months and 1 year.nnnCONCLUSIONSnAldosterone breakthrough is a frequent event 1 year after initiating renin-angiotensin-aldosterone system blockade, particularly in participants exposed to intensive lowering of BP with sodium depletion and short-acting angiotensin II receptor blockers. Short-term serum aldosterone level increases at 6 months are not associated with negative kidney outcomes between 6 months and 1 year.

Creatinine‐based equations for the adjustment of drug dosage in an obese population

AIMnFor drug dosing adaptation, the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend using estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, after de-indexation by body surface area (BSA). In pharmacology, the Cockcroft-Gault (CG) equation is still recommended to adapt drug dosage. In the context of obesity, adjusted ideal body weight (AIBW) is sometimes preferred to actual body weight (ABW) for the CG equation. The aim of the present study was to compare the performance of the different GFR-estimating equations, non-indexed or de-indexed by BSA for the purpose of drug-dosage adaptation in obese patients.nnnMETHODSnWe analysed data from patients with a body mass index (BMI) higher than 30 kg m(-2) who underwent a GFR measurement. eGFR was calculated using the CKD-EPI and Modification of Diet in Renal Disease (MDRD) equations, de-indexed by BSA, and the CG equation, using either ABW, AIBW or lean body weight (LBW) for the weight variable and compared with measured GFR, expressed in ml min(-1).nnnRESULTSnIn our population of obese patients, use of the AIBW instead of the ABW in the CG equation, markedly improved the overall accuracy of this equation [57% for CGABW and 79% for CGAIBW (P < 0.05)]. For high BMI (over 40 kg m(-2)), the accuracy of the CG equations is no different when using LBW than when using AIBW. The MDRD and CKD-EPI equations de-indexed by the BSA also performed well, with an overall higher accuracy for the MDRD de-indexed equation [(80% and 76%, respectively (P < 0.05)].nnnCONCLUSIONSnThe de-indexed MDRD equation appeared to be the most suitable for estimating the non-indexed GFR for the purpose of drug dosage adaptation in obese patients.

Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance

BACKGROUNDnMinimal-change nephrotic syndrome (MCNS) is a common cause of steroid sensitive nephrotic syndrome (NS) with frequent relapse. Although steroids and calcineurin inhibitors (CNIs) are the cornerstone treatments, the use of rituximab (RTX), a monoclonal antibody targeting B cells, is an efficient and safe alternative in childhood.nnnMETHODSnBecause data from adults remain sparse, we conducted a large retrospective and multicentric study that included 41 adults with MCNS and receiving RTX.nnnRESULTSnComplete (NS remission and withdrawal of all immunosuppressants) and partial (NS remission and withdrawal of at least one immunosuppressants) clinical responses were obtained for 25 and 7 patients, respectively (overall response 78%), including 3 patients that only received RTX and had a complete clinical response. After a follow-up time of 39 months (6-71), relapses occurred in 18 responder patients [56%, median time 18 months (3-36)]. Seventeen of these received a second course of RTX and then had a complete (n = 13) or partial (n = 4) clinical response. From multivariate analysis, on-going mycophenolate mofetil (MMF) therapy at the time of RTX was the only predictive factor for RTX failure [HR = 0.07 95% CI (0.01-0.04), P = 0.003]. Interestingly, nine patients were still in remission at 14 months (3-36) after B-cell recovery. No significant early or late adverse event occurred after RTX therapy.nnnCONCLUSIONSnRTX is safe and effective in adult patients with MCNS and could be an alternative to steroids or CNIs in patients with a long history of relapsing MCNS.