The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy.

A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.

Prognostic models for chronic kidney disease: a systematic review and external validation.

BACKGROUND: Accurate risk prediction is needed in order to provide personalized healthcare for chronic kidney disease (CKD) patients. An overload of prognosis studies is being published, ranging from individual biomarker studies to full prediction studies. We aim to systematically appraise published prognosis studies investigating multiple biomarkers and their role in risk predictions. Our primary objective was to investigate if the prognostic models that are reported in the literature were of sufficient quality and to externally validate them. METHODS: We undertook a systematic review and appraised the quality of studies reporting multivariable prognosis models for end-stage renal disease (ESRD), cardiovascular (CV) events and mortality in CKD patients. We subsequently externally validated these models in a randomized trial that included patients from a broad CKD population. RESULTS: We identified 91 papers describing 36 multivariable models for prognosis of ESRD, 50 for CV events, 46 for mortality and 17 for a composite outcome. Most studies were deemed of moderate quality. Moreover, they often adopted different definitions for the primary outcome and rarely reported full model equations (21% of the included studies). External validation was performed in the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners trial (n = 788, with 160 events for ESRD, 79 for CV and 102 for mortality). The 24 models that reported full model equations showed a great variability in their performance, although calibration remained fairly adequate for most models, except when predicting mortality (calibration slope >1.5). CONCLUSIONS: This review shows that there is an abundance of multivariable prognosis models for the CKD population. Most studies were considered of moderate quality, and they were reported and analysed in such a manner that their results cannot directly be used in follow-up research or in clinical practice.

Referring patients with stable moderate-to-advanced chronic kidney disease back to primary care: a feasibility study.

BACKGROUND: Care for patients with chronic kidney disease (CKD) necessitates tailored pathways between primary and secondary care. It is unknown if back referring patients with CKD is safe and effective. AIM: To study the feasibility of discharging patients with stable moderate-to-advanced CKD from secondary to primary care, and to evaluate quality of care (QoC) and patients' and GPs' experiences. DESIGN & SETTING: A monocentre prospective mixed-method study in the Netherlands. METHOD: Patients were included who met pre-determined back-referral (BR) criteria. Patients were discharged with personalised information guides and transfer letters. GPs had the option of consulting a nephrologist by telenephrology. Renal outcomes, QoC, and experiences were collected after 1 year. RESULTS: Eighteen patients were included. The mean age was 73 years; the mean estimated glomerular filtration rate (eGFR) was 33.2 ml/min/1.73 m2 at baseline. After 1 year, four patients had received either no or incomplete monitoring, and one patients' blood pressure was too high. The remaining 13 had stable eGFR, proteinuria, and metabolic parameters. Patients were satisfied with information provision and treatment by GPs but expected more frequent monitoring. In one-third of cases, monitoring frequency was decreased by GPs for several reasons. GPs believed they had sufficient knowledge to treat patients with CKD, but indicated they needed support besides a transfer letter. CONCLUSION: BR seems safe and feasible for patients with stable moderate-to-advanced CKD who meet specific criteria. Patients have good renal outcomes after 1 year and are satisfied with treatment. GP QoC can be improved, particularly completeness and monitoring frequency.

MASTERPLAN: study of the role of nurse practitioners in a multifactorial intervention to reduce cardiovascular risk in chronic kidney disease patients.

Moderate to severe chronic kidney disease (CKD) is associated with increased cardiovascular risk. Usually nephrologists are primarily responsible for the care of CKD patients. However, in many cases treatment goals, as formulated in guidelines, are not met. The addition of a nurse practitioner might improve the quality of care. The Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study is a randomized controlled multicenter trial, aimed at investigating whether a multifactorial approach in patients with moderate to severe CKD (stage 3 and 4) to achieving treatment goals using both a polydrug strategy and lifestyle treatment either with or without the addition of a nurse practitioner will reduce cardiovascular risk and slow the decline of kidney function. Patients (n=793) have been randomized to nurse care or physician care. In the nurse-care arm of the study, nurse practitioners use flowcharts to address risk factors requiring drug and/or lifestyle modification. They have been trained to coach patients by motivational interviewing with the aim of improving patient self-management. At baseline, both treatment groups show equal distributions with regard to key variables in the study. Moreover, in only 1 patient were all risk factors within the limits as defined in various guidelines, which underscores the relevance of our initiative.

Membranous nephropathy in the older adult: epidemiology, diagnosis and management.

Membranous nephropathy is the most important cause of the nephrotic syndrome in elderly patients (aged >65 years). The clinical presentation is similar in older and younger patients, although elderly patients more often present with renal failure. Notably, glomerular filtration rate (GFR) is usually lower in the elderly due to the physiological decline in GFR after the age of 30 years. Secondary causes, especially malignancies, are more common in older patients with membranous nephropathy. Therefore, elderly patients should undergo a thorough examination to exclude a secondary cause. The prognosis of elderly patients with idiopathic membranous nephropathy is not very different from that of younger patients. All elderly patients should receive symptomatic treatment aimed at reducing hypertension, oedema, proteinuria and hyperlipidaemia. It is recommended that elderly patients with a low serum albumin (<2 g/dL) receive prophylactic anticoagulation because of a high risk for thrombosis. Immunosuppressive therapy should be reserved for elderly patients at high risk of progression to end-stage renal disease because the elderly are particularly prone to the adverse effects and infectious complications of immunosuppressive therapy. High-risk elderly patients are characterised by renal insufficiency (GFR <45 mL/min/1.73m(2)), an increase in serum creatinine of >25% or a severe persistent nephrotic syndrome not responding to symptomatic treatment. In addition, elderly patients with a relatively normal GFR (>or=45 mL/min/1.73m(2)) and high urinary excretion of beta(2)-microglobulin and IgG are also at increased risk of developing end-stage renal disease; however, the deterioration in renal function is usually a slow process. Therefore, such patients benefit from immunosuppressive therapy only if their life expectancy is good. If immunosuppressive therapy is started, first-line treatment consists of prednisone and cyclophosphamide. If cyclophosphamide is contraindicated or fails to induce a remission, ciclosporin could be used. Treatment with ciclosporin should be limited to patients with a relatively normal renal function (GFR >60 mL/min/1.73m(2)) in view of its nephrotoxicity in patients with renal dysfunction.

Impact on cardiovascular risk follow-up from a shift to the CKD-EPI formula for eGFR reporting: a cross-sectional population-based primary care study.

OBJECTIVE: To assess the impact on cardiovascular risk factor management in primary care by the introduction of chronic kidney disease epidemiological collaboration (CKD-EPI) for estimated-glomerular filtration rate (eGFR) reporting. DESIGN AND SETTING: Cross-sectional study of routine healthcare provision in 47 primary care practices in The Netherlands with Modification of Diet and Renal Disease Study eGFR reporting. METHODS: eGFR values were recalculated using CKD-EPI in patients with available creatine tests. Patients reclassified from CKD stage 3a to CKD stage 2 eGFR range were compared to those who remained in stage 3a for differences in demographic variables, blood pressure, comorbidity, medication usage and laboratory results. RESULTS: Among the 60 673 adult patients (37% of adult population) with creatine values, applying the CKD-EPI equation resulted in a 16% net reduction in patients with CKD stage 3 or worse. Patients reclassified from stage 3a to 2 had lower systolic blood pressure (139.7 vs 143.3 mm Hg p<0.0001), higher diastolic blood pressure (81.5 vs 78.4 mm Hg p<0.0001) and higher cholesterol (5.4 vs 5.1 mmol/L p<0.0001) compared to those who remained in stage 3a. Of those reclassified out of a CKD diagnosis 463 (32%) had no comorbidities that would qualify for annual CVD risk factor assessment and 20 (12% of those with sufficient data) had a EuroSCORE CVD risk >20% within 10 years. CONCLUSIONS: Use of the CKD-EPI equation will result in many patients being removed from CKD registers and the associated follow-up. Current risk factor assessment in this group may be lacking from routine data and some patients within this group are at an increased risk for cardiovascular events.

Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome in patients with membranous nephropathy.

BACKGROUND: The course of idiopathic membranous nephropathy (iMN) is variable in untreated patients. Accurate prediction of renal outcome would allow optimal treatment decisions. We demonstrated that urinary beta2-microglobulin (beta2M) predicted prognosis in iMN with high sensitivity and specificity. It has been suggested that focal segmental glomerulosclerosis (FSGS) is a discriminative parameter with independent prognostic value. METHODS: We selected patients with iMN biopsied between 1988 and 2002. Biopsies were analysed for the presence of FSGS, interstitial fibrosis and vascular lesions. Serum creatinine, creatinine clearance, proteinuria and blood pressure were recorded at baseline. Outcome variables included remission of proteinuria, renal death (RD) defined as serum creatinine >135 micromol/l or increase of serum creatinine of >50%, or end-stage renal disease (ESRD). In a subgroup of patients, urinary beta2-microglobulin (beta2M) was measured. RESULTS: We included 53 patients (33M, 20F). Mean age was 51 years, serum creatinine 99 micromol/l, and proteinuria 7.0 g/10 mmol creatinine. FSGS was present in 22 patients. These patients were characterized by a higher serum creatinine at time of biopsy (P = 0.035), more severe interstitial fibrosis (P = 0.001) and higher stage of membranous nephropathy (P = 0.001). During follow-up 24 patients developed RD, almost equally distributed between patients with and without FSGS. Renal survival was numerically, but not significantly, lower in patients with FSGS. In Cox proportional hazard analysis, only serum creatinine at the time of biopsy was an independent predictor of RD or ESRD (P < 0.001). In patients with known urinary beta2M, there was no significant correlation with FSGS score (P = 0.174). CONCLUSION: FSGS is not an accurate prognostic marker in iMN. Histological scoring of FSGS is inferior to measurement of urinary proteins in predicting renal outcome in iMN.