Temporal validation of the CT-PIRP prognostic model for mortality and renal replacement therapy initiation in chronic kidney disease patients.

BACKGROUND: A classification tree model (CT-PIRP) was developed in 2013 to predict the annual renal function decline of patients with chronic kidney disease (CKD) participating in the PIRP (Progetto Insufficienza Renale Progressiva) project, which involves thirteen Nephrology Hospital Units in Emilia-Romagna (Italy). This model identified seven subgroups with specific combinations of baseline characteristics that were associated with a differential estimated glomerular filtration rate (eGFR) annual decline, but the model's ability to predict mortality and renal replacement therapy (RRT) has not been established yet. METHODS: Survival analysis was used to determine whether CT-PIRP subgroups identified in the derivation cohort (n = 2265) had different mortality and RRT risks. Temporal validation was performed in a matched cohort (n = 2051) of subsequently enrolled PIRP patients, in which discrimination and calibration were assessed using Kaplan-Meier survival curves, Cox regression and Fine & Gray competing risk modeling. RESULTS: In both cohorts mortality risk was higher for subgroups 3 (proteinuric, low eGFR, high serum phosphate) and lower for subgroups 1 (proteinuric, high eGFR), 4 (non-proteinuric, younger, non-diabetic) and 5 (non-proteinuric, younger, diabetic). Risk of RRT was higher for subgroups 3 and 2 (proteinuric, low eGFR, low serum phosphate), while subgroups 1, 6 (non-proteinuric, old females) and 7 (non-proteinuric, old males) showed lower risk. Calibration was excellent for mortality in all subgroups while for RRT it was overall good except in subgroups 4 and 5. CONCLUSIONS: The CT-PIRP model is a temporally validated prediction tool for mortality and RRT, based on variables routinely collected, that could assist decision-making regarding the treatment of incident CKD patients. External validation in other CKD populations is needed to determine its generalizability.

"Troponinosis", the Cardiologist's Curse-When Clinic-Laboratory Interaction Unveils the Mystery: A Case Report.

Cardiac troponins are key diagnostic and prognostic biomarkers in acute myocardial infarction and, more generally, for the detection of myocardial injury. Since the introduction of the first immunochemistry methods, there has been a remarkable evolution in analytical performance, especially concerning a progressive improvement in sensitivity. However, the measurement of circulating troponins remains rarely susceptible to analytical interferences. We report a case of persistently elevated troponin I concentrations in a patient with known ischemic heart disease, which almost led to unnecessary diagnostic-therapeutic interventions. A prompt laboratory consultation by the cardiologist ultimately led to the identification of an analytical interference due to troponin macrocomplexes (macrotroponin) causing elevated troponin values in the absence of a clinical presentation compatible with myocardial damage.

[Apheresis in the treatment of vasculitis]. / Aferesi nelle vasculiti.

ANCA-associated vasculitides are a group of inflammatory diseases affecting medium and small vessels with a redundant and hence complex pathogenetic mechanism. Since their first identification, their dismal prognosis has forced researchers to find effective therapies. The prognosis has changed since the advent of immunomodulatory drugs like steroids, cyclophosphamide, azathioprine, mycophenolate mofetil and, more recently, biological drugs. Plasmapheresis in association with immune suppressant drugs has shown beneficial effects in some clinical trials, mostly in dialysis-dependent patients. Apheresis should remove, in a nonselective manner, pathogenetic antibodies like ANCA but also immune complexes, cytokines and inflammatory mediators. A recent meta-analysis took into account 28 randomized clinical trials studying therapeutic interventions in adult vasculitis with renal involvement, six of them scheduling plasmapheresis as adjunctive therapy to immune suppressant drugs. This association significantly reduced the need for dialysis at three (1 trial: RR 0.45, 95% CI 0.24-0.84) and twelve (5 trials: RR 0.47, 95% CI 0.3-0.75) months but not the mortality at one year. We can conclude that plasmapheresis is an effective treatment option for vasculitides with severe renal failure. It can also be considered in case of ineffectiveness of or contraindications to standard treatment.

[Plasma cell dyscrasias and renal damage]. / Il coinvolgimento del rene nelle discrasie plasmacellulari.

Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.

[The accuracy of hospital discharge records and their use in identifying and staging chronic kidney disease].

Administrative databases contain precious information that can support the identification of specific pathologies. Specifically, chronic kidney disease (CKD) patients could be identified using hospital discharge records (HDR); these should contain information on the CKD stage using subcategories of the ICD9-CM classification's 585 code (subcategories can be expressed just by adding a fourth digit to this code). To verify the accuracy of HDR data regarding the coding of CKD collected in the Italian region Emilia-Romagna, we analyzed the HDR records of patients enrolled in the PIRP project, which could easily be matched with eGFR data obtained through laboratory examinations. The PIRP database was used as the gold standard because it contains data on CKD patients followed up since 2004 in thirteen regional nephrology units and includes data obtained from reliable and homogeneous laboratory measurement. All HDR of PIRP patients enrolled between 2009 and 2017 were retrieved and matched with available laboratory data on eGFR, collected within 15 days before or after discharge. We analyzed 4.168 HDR, which were classified as: a) unreported CKD (n=1.848, 44.3%); b) unspecified CKD, when code 585.9 (CKD, not specified) or 586 was used (n=446, 10.7%); c) wrong CKD (n=833, 20.0%); d) correct CKD (n=1041, 25.0%). We noticed the proportion of unreported CKD growing from 32.9% in 2009 to 56.6% in 2017, and the correspondent proportion of correct CKDs decreasing from 25.4% to 22.3%. Across disciplines, Nephrology showed the highest concordance (69.1%) between the CKD stage specified in the HDRs and the stage reported in the matched laboratory exam, while none of the other disciplines, except for Geriatrics, reached 20% concordance. When the CKD stage was incorrectly coded, it was generally underestimated; among HDRs with unreported or unspecified CKD at least half of the discharges were matched with lab exams reporting CKD in stage 4 or 5. We found that the quality of CKD stage coding in the HDR record database was very poor, and insufficient to identify CKD patients unknown to nephrologists. Moreover, the growing proportion of unreported CKD could have an adverse effect on patients' timely referral to a nephrologist, since general practitioners might remain unaware of their patients' illness. Actions aimed at improving the training of the operators in charge of HDRs compilation and, most of all, at allowing the exploitation of the informative potential of HDRs for epidemiological research are thus needed.

[Smart, Social, and Mobile: the future of Nephrology in the Era of Digital Health]. / Smart, Social e Mobile: la Nefrologia nell'era della Sanità digitale.

Healthcare is in the middle of a digital revolution. Physicians are adopting mobile apps that make them more effective and patients are taking to ones that give them more control over their healthcare. Mobile technology is changing Medicine. A new movement for free open access medical education (FOAMed) is growing through Social Media. E-learning is increasing access to new and exciting learning opportunities, deeply changing the traditional concept of continuous medical education. What will be the future of Nephrology in the era of Digital Health?

A novel option for reducing free light chains in myeloma kidney: supra-hemodiafiltration with endogenous reinfusion (HFR).

BACKGROUND: In myeloma cast nephropathy, fast reduction of serum free light chain (FLC) levels correlates with renal recovery. Recently, extracorporeal treatments using filters with a high-molecular weight cut-off have been successfully used for FLC removal. However, using these new filters, high cost and elevated albumin leakage are common drawbacks. We studied a new and cheaper therapeutic approach with adsorbent resins to evaluate its efficacy. METHODS: We treated four patients, affected by dialysis-dependent acute kidney injury (AKI) due to biopsy proven de novo FLC myeloma cast nephropathy. Each patient underwent bortezomib chemotherapy and extracorporeal treatment with the supra-hemodiafiltration with endogenous reinfusion (HFR) technique (Supra-HFR, Bellco Mirandola, Modena, Italy). Supra-HFR is a kind of hemodiafiltration that utilizes separated convection, diffusion and adsorption. The sorbent cartridge has a high affinity for FLC (both κ and λ) but is able to re-infuse albumin, avoiding the need for albumin perfusions. Supra HFR treatments (4 h each) were carried out for eight consecutive days and then every other day. RESULTS: All patients showed a significant reduction of serum FLC, whereas serum albumin concentration remained unchanged. Renal function recovered in three out of four patients. CONCLUSIONS: FLC removal with adsorbent resins represents an effective therapeutic strategy that does not require replacement with albumin .